Tryptophan, serotonin, and aging
色氨酸,血清素和衰老
by Raymond Peat
Beginning with the industrial production of glutamic acid (sold as MSG, monosodium glutamate), the public has been systematically misinformed about the effects of amino acids in the diet. The FDA has been industry's powerful ally in misleading the public. Despite research that clearly showed that adults assimilate whole proteins more effectively than free amino acids, much of the public has been led to believe that “predigested” hydrolized protein and manufactured free amino acids are more easily assimilated than real proteins, and that they are not toxic. Even if free amino acids could be produced industrially without introducing toxins and allergens, they wouldn't be appropriate for nutritional use.
从谷氨酸(以味精、谷氨酸钠出售)的工业化生产开始,公众就被系统性地误导了,对饮食中氨基酸的影响。在误导公众方面,FDA一直是食品工业的有力盟友。尽管研究清楚地表明,成年人吸收全蛋白质比吸收游离氨基酸更有效,但许多公众一直被误导,认为“预先消化”的水解蛋白质和合成的游离氨基酸比真正的蛋白质更容易被吸收,而且它们是无毒的。即使游离氨基酸可以工业化生产而不引入毒素和过敏原,它们也不适合用于营养用途。
Although some research shows that babies up to the age of 18 months can assimilate free amino acids, a baby formula containing hydrolyzed protein was associated with decreased serum albumin, which suggests that it interfered with protein synthesis.
尽管一些研究表明18个月以下的婴儿可以吸收游离氨基酸,但含有水解蛋白的婴儿配方奶粉与血清白蛋白减少有关,这表明它干扰了蛋白质的合成。
The myth that free amino acids are “natural nutritional substances” has been used to promote the use of many products besides MSG, including aspartame, chelated minerals, and tryptophan.
游离氨基酸是“天然营养物质”的神话已经被用来推广味精以外的许多产品的使用,包括阿斯巴甜、螯合矿物质和色氨酸。
Although several amino acids can be acutely or chronically toxic, even lethal, when too much is eaten, tryptophan is the only amino acid that is also carcinogenic. (It can also produce a variety of toxic metabolites, and it is very susceptible to damage by radiation.) Since tryptophan is the precursor of serotonin, the amount of tryptophan in the diet can have important effects on the way the organism responds to stress, and the way it develops, adapts, and ages.
虽然有些氨基酸可能会急性或慢性中毒,甚至致命,但过量食用时,色氨酸是唯一一种致癌的氨基酸。(它还能产生各种有毒的代谢物,而且很容易受到辐射的损害。)由于色氨酸是血清素的前体,饮食中色氨酸的含量对机体应对压力、发育、适应和衰老的方式有重要影响。
When an inflammatory disease (eosinophilia-myalgia syndrome) was noticed in people using tryptophan tablets (1989-90), there was an intense campaign to exonerate the tryptophan itself by blaming the reaction on an impurity in one company's product. But the syndrome didn't occur only in the people who used that company's product, and similar changes can be produced by a high-tryptophan diet (Gross, et al., 1999).
当使用色氨酸片剂的人出现炎症(嗜酸性肌痛综合征)时(1989-90),一场激烈的运动将色氨酸本身的反应归咎于某公司产品中的杂质,从而为其辩护。但该综合征并不只发生在使用该公司产品的人身上,高色氨酸饮食也会产生类似的变化(Gross等人,1999)。
There are people who advocate the use of tryptophan supplementation or other means to increase serotonin in the tissues as a treatment for the fibromyalgia syndrome, but the evidence increasingly suggests that excessive serotonin, interfering with muscle mitochondria, is a major factor in the development of that syndrome.
有人提倡使用色氨酸补充剂或其他方法来增加组织中的血清素,以治疗纤维肌痛综合征,但越来越多的证据表明,过量的血清素干扰肌肉线粒体,是该综合征发展的一个主要因素。
In 1965, Hans Selye showed that the injection of serotonin caused muscular dystrophy. Subsequent studies suggest that serotonin excess is involved in both muscular and nervous dystrophy or degeneration. (O'Steen, 1967; Narukami, et al., 1991; Hanna and Peat, 1989.)
1965年,Hans Selye证明注射血清素会导致肌肉萎缩。随后的研究表明,血清素过量与肌肉和神经营养不良或退化有关。(1967;鸣等人,1991;Hanna和Peat, 1989年)。
The fatigue produced by “over-training” is probably produced by a tryptophan and serotonin overload, resulting from catabolism of muscle proteins and stress-induced increases in serotonin. Muscle catabolism also releases a large amount of cysteine, and cysteine, methionine, and tryptophan suppress thyroid function (Carvalho, et al., 2000). Stress also liberates free fatty acids from storage, and these fatty acids increase the uptake of tryptophan into the brain, increasing the formation of serotonin. Since serotonin increases ACTH and cortisol secretion, the catabolic state tends to be self-perpetuating. This process is probably a factor influencing the rate of aging, and contributing to the physiological peculiarities of aging and depression.
“过度训练”产生的疲劳很可能是由色氨酸和血清素超载产生的,这是由肌肉蛋白质的分解代谢和压力引起的血清素增加造成的。肌肉分解代谢也释放大量的半胱氨酸,而半胱氨酸、蛋氨酸和色氨酸抑制甲状腺功能(Carvalho, et al., 2000)。压力也释放了储存的游离脂肪酸,这些脂肪酸增加了大脑对色氨酸的吸收,增加了血清素的形成。由于血清素增加ACTH和皮质醇的分泌,分解代谢状态趋向于自我延续。这一过程可能是影响衰老速度的一个因素,并有助于衰老和抑郁的生理特性。
Malnutrition, and specifically protein deficiency, produces an inflammatory state that involves extreme serotonin dominance. Stress or malnutrition prenatally or in infancy leads to extreme serotonin dominance in adulthood. Other functions of tryptophan are reduced, as more of it is turned into serotonin.
营养不良,特别是蛋白质缺乏,会产生一种炎症状态,这种状态涉及到极端的血清素支配。产前或婴儿时期的压力或营养不良会导致成年后血清素的极端支配。色氨酸的其他功能减弱,因为更多色氨酸被转化为血清素。
Decreasing tryptophan or decreasing serotonin improves learning and alertness, while increased serotonin impairs learning.
减少色氨酸或减少血清素可以提高学习能力和警觉性,而增加血清素则会损害学习能力。
Tryptophan is an essential amino acid for reproduction and growth of the young animal. Most research on the nutritional requirements for amino acids has been done on farm animals, because of the economic incentive to find the cheapest way to produce the fastest growth. Farmers aren't interested in the nutritional factors that would produce the longest-lived pigs. Some research has been done on the amino acid requirements of rats over a significant part of their short lifespans. In rats and farm animals, the amount of tryptophan required decreases with time as the rate of growth slows.
色氨酸是幼动物繁殖和生长所必需的氨基酸。大多数关于氨基酸营养需求的研究都是在农场动物身上进行的,因为经济诱因是寻找最便宜的方法以获得最快的增长。农民们对生产寿命最长的猪的营养因素不感兴趣。在老鼠短暂的寿命中,有相当一部分对氨基酸的需求进行了研究。在大鼠和农场动物中,色氨酸的需求量随着生长速度的减慢而随着时间的推移而减少。
In some ways, rats never really mature, since they keep growing for nearly their whole lifespan. Their growth stops just a short time before they die, which is usually around the age of two or three years. (At this age, rats' cells still retain approximately the same high water content seen in the cells of a two year-old child.) They usually become infertile about half-way through their lifespan. If we try to draw conclusions about amino acid requirements from the rat studies, I think we would want to extrapolate the curve for the decreasing need for tryptophan, far beyond the point seen during the rat's short life. And those “requirements” were determined according to the amounts that produced a maximum rate of growth, using the index of the pig farmers, as if the rats were being studied for possible use as meat.
在某些方面,老鼠永远不会真正成熟,因为它们在几乎整个生命周期中都在生长。它们的生长在死亡前很短的一段时间内停止,通常是在两三岁左右。(在这个年龄,老鼠的细胞仍然保持大约两岁儿童细胞的高含水量。)它们通常在寿命的一半左右变得不能生育。如果我们试图从老鼠的研究中得出氨基酸需求的结论,我想我们会推断出色氨酸需求减少的曲线,远远超出老鼠短暂生命中看到的点。而这些“需求”是根据产生最大生长率的数量来确定的,使用的是养猪户的指数,就好像是在研究老鼠是否可以用作肉一样。
When rats were fed a diet completely lacking tryptophan for a short period, or a diet containing only one fourth of the “normal” amount for a more prolonged period, the results were surprising: They kept the ability to reproduce up to the age of 36 months (versus 17 months for the rats on the usual diet), and both their average longevity and their maximum longevity increased significantly. They looked and acted like younger rats. (A methionine-poor diet also has dramatic longevity-increasing effects.)
当老鼠在短时间内完全缺乏色氨酸,或在更长时间内只含有“正常”量的四分之一的饮食时,结果令人惊讶:它们的繁殖能力一直保持到36个月大(而正常饮食的老鼠只有17个月大),它们的平均寿命和最大寿命都显著增加。它们看起来和行为都像年轻的老鼠。(缺乏蛋氨酸的饮食也有显著的长寿效果。)
On the tryptophan-poor diet, the amount of serotonin in the brain decreased. When brain serotonin decreases, the level of testosterone in male animals increases. More than 20 years ago, a chemical (p-chlorophenylalanine) that inhibits serotonin synthesis was found to tremendously increase libido.
在缺乏色氨酸的饮食中,大脑中血清素的数量减少了。当大脑血清素减少时,雄性动物的睾丸激素水平就会增加。20多年前,人们发现一种化学物质(对氯苯丙氨酸)可以抑制血清素的合成,从而极大地提高性欲。
In old age, the amount of serotonin in the brain increases. This undoubtedly is closely related to the relative inability to turn off cortisol production that is characteristic of old age (Sapolsky and Donnelly, 1985). Hypothyroidism increases the formation of serotonin, as does cortisol (Henley, et al., 1997, 1998; Neckers and Sze, 1976).
随着年龄的增长,大脑中血清素的含量会增加。毫无疑问,这与老年特有的相对不能停止皮质醇的产生密切相关(Sapolsky和Donnelly, 1985)。甲状腺机能减退会增加血清素的形成,皮质醇也是如此(Henley等人,1997,1998;Neckers and Sze, 1976)。
In white hair, the amount of tryptophan is higher than in hair of any other color. Although serotonin and tryptophan are very important during rapid growth, their presence in senile tissues is probably closely associated with the processes of decline. The hair loss that occurs in hypothyroidism, postpartum syndrome, and with the use of drugs such as St. John's wort (which can also cause the “serotonin syndrome”) could be another effect of excess serotonin.
在白发中,色氨酸的含量高于任何其他颜色的头发。虽然血清素和色氨酸在快速生长过程中非常重要,但它们在老年性组织中的存在可能与衰老过程密切相关。甲状腺功能减退症、产后综合症以及服用圣约翰草(也能导致“血清素综合症”)等药物导致的脱发可能是血清素过量的另一个影响。
Serotonin stimulates cell division and tends to increase the formation of connective tissue, so its formation should be closely regulated once full growth is achieved. It contributes to the age- or stress-related thickening of blood vessels, and other fibrotic processes that impair organ function.
血清素(5-羟色胺)刺激细胞分裂,并倾向于增加结缔组织的形成,因此,一旦完全生长完成,它的形成应该受到密切的调控。它会导致与年龄或压力相关的血管增厚,以及其他损害器官功能的纤维化过程。
The metabolic rate (eating more without gaining extra weight) and ability to regulate body temperature are increased by early tryptophan deprivation. (Ashley and Curzon, 1981; Segall and Timiras, 1975.) The ability to oxidize sugar is impaired by serotonin, and several drugs with antiserotonin actions are being used to treat diabetes and its complications, such as hypertension, obesity, and foot ulcers.
早期色氨酸剥夺会提高代谢率(吃得更多而不增重)和调节体温的能力。(Ashley and Curzon, 1981年;西格尔和蒂米拉斯,1975年。)血清素削弱了人氧化糖的能力,几种具有抗血清素作用的药物被用于治疗糖尿病及其并发症,如高血压、肥胖和足溃疡。
An excess of tryptophan early in life, stress, or malnutrition, activates the system for converting tryptophan into serotonin, and that tendency persists into adulthood, modifying pituitary function, and increasing the incidence of pituitary and other cancers.
在生命早期,如果色氨酸过量、压力或营养不良,就会激活色氨酸转化为血清素的系统,这种趋势会持续到成年,改变脑垂体功能,增加脑垂体和其他癌症的发病率。
Serotonin's contribution to high blood pressure is well established. It activates the adrenal cortex both directly and through activation of the pituitary. It stimulates the production of both cortisol and aldosterone. It also activates aldosterone secretion by way of the renin-angiotensin system. Angiotensin is an important promoter of inflammation, and contributes to the degeneration of blood vessels with aging and stress. It can also promote estrogen production.
血清素对高血压的影响已被证实。它可以直接激活肾上腺皮质,也可以通过激活脑垂体来激活。它刺激皮质醇和醛固酮的产生。它还通过肾素-血管紧张素系统激活醛固酮的分泌。血管紧张素是炎症的重要促进剂,随着年龄的增长和压力的增加,血管发生退行性变。它还可以促进雌激素的产生。
In the traditional diet, rather than just eating muscle meats, all the animal parts were used. Since collagen makes up about 50% of the protein in an animal, and is free of tryptophan, this means that people were getting about half as much tryptophan in proportion to other amino acids when they used foods such as “head cheese,” ox-tails, and chicken feet.
在传统饮食中,不只是吃肌肉,所有的动物部位都被使用。由于胶原蛋白约占动物蛋白质的50%,而且不含色氨酸,这意味着当人们食用“头芝士”、牛尾和鸡爪等食物时,色氨酸与其他氨基酸的比例大约是原来的一半。
While some of the toxic effects of an excess of individual amino acids have been investigated, and some of the protective or harmful interactions resulting from changing the ratios of the amino acids have been observed, the fact that there are about 20 amino acids in our normal diet means that there is an enormous number of possibilities for harmful or beneficial interactions.
虽然已经研究了过量的单个氨基酸的一些毒性作用,也观察到了由于改变氨基酸比例而产生的一些保护性或有害的相互作用,事实上,在我们的日常饮食中大约有20种氨基酸,这意味着存在着大量有害或有益的相互作用的可能性。
The optimal quantity of protein in the diet has traditionally been treated as if it were a matter that could be resolved just by observing the rate of growth when a certain protein is given in certain quantities, along with “standard amounts” of calories and other nutrients. This kind of research has been useful to farmers who want to find the cheapest foods that will produce the biggest animals in the shortest time. But that kind of research climate has spread a degraded concept of nutrition into the culture at large, influencing medical ideas of nutrition, the attitudes of consumers, and the policies of governmental regulatory agencies.
传统上,人们一直认为,饮食中蛋白质的最佳数量,似乎只要观察特定数量的蛋白质以及“标准数量”的卡路里和其他营养物质的生长速度,就能解决这个问题。这种研究对那些想要在最短时间内生产出最大动物的最便宜食物的农民很有用。但是,这种研究氛围已经把一种退化的营养概念传播到整个文化中,影响了营养的医学观念、消费者的态度和政府监管机构的政策。
When synthetic amino acids are used to supplement natural proteins, they are usually chosen according to irrelevant models of the “ideal protein's” composition, and many toxic contaminants are invariably present in the synthetic free amino acids.
当合成氨基酸用于补充天然蛋白质时,它们通常是根据“理想蛋白质”组成的无关模型来选择的,而且许多有毒污染物总是存在于合成的游离氨基酸中。
For the present, the important thing is to avoid the use of the least appropriate food products, while choosing natural foods that have historical, epidemiological, and biochemical justification.
就目前而言,重要的是避免使用最不合适的食品产品,同时选择具有历史、流行病学和生化理由的天然食品。
Whey has been promoted as a protein supplement, but it contains a slightly higher proportion of tryptophan than milk does. Cheese (milk with the whey removed) contains less tryptophan. Some people have been encouraged to eat only the whites of eggs, “to avoid cholesterol,” but the egg albumin is rich in tryptophan.
乳清被推广为蛋白质补充剂,但它所含色氨酸的比例比牛奶略高。奶酪(除去乳清的牛奶)含有较少的色氨酸。有些人被鼓励只吃蛋清,“以避免胆固醇”,但蛋清富含色氨酸。
The expensive tender cuts of meat contain excessive amounts of cysteine and tryptophan, but bone broth (gelatin) and the tougher cuts of meat contain more gelatin, which lacks those amino acids. Many fruits are deficient in tryptophan, yet have very significant quantities of the other amino acids. They also contain some of the “carbon skeleton” (keto-acid) equivalents of the essential amino acids, which can be converted to protein in the body.
昂贵的嫩肉块含有过量的半胱氨酸和色氨酸,但骨汤(明胶)和较硬的肉块含有更多的明胶,而明胶缺乏这些氨基酸。许多水果缺乏色氨酸,但其他氨基酸的含量却非常高。它们还含有一些必需氨基酸的“碳骨架”(酮酸),可以在体内转化为蛋白质。
Serotonin excess produces a broad range of harmful effects: Cancer, inflammation, fibrosis, neurological damage, shock, bronchoconstriction, and hypertension, for example. Increased serotonin impairs learning, serotonin antagonists improve it.
血清素过量会产生广泛的有害影响:例如癌症、炎症、纤维化、神经损伤、休克、支气管收缩和高血压。增加会损害学习能力,血清素拮抗剂会改善学习能力。
The simplest, nonessential, amino acid, glycine, has been found to protect against carcinogenesis, inflammation, fibrosis, neurological damage, shock, asthma, and hypertension. Increased glycine improves learning (Handlemann, et al., 1989; File, et al., 1999), glycine antagonists usually impair it. Its antitoxic and cytoprotective actions are remarkable. Collagen, besides being free of tryptophan, contains a large amount of glycine–32% of its amino acid units, 22% of its weight.
最简单的、非必需的氨基酸,甘氨酸,已被发现可以预防癌变、炎症、纤维化、神经损伤、休克、哮喘和高血压。增加甘氨酸可改善学习(Handlemann等,1989;文件,等,1999),甘氨酸拮抗剂通常损害它。其抗毒性和细胞保护作用显著。胶原蛋白除了不含色氨酸外,还含有大量的甘氨酸——占其氨基酸单位的32%,占其重量的22%。
The varied antiinflammatory and protective effects of glycine can be thought of as an antiserotonin action. For example, serotonin increases the formation of TNF (tumor necrosis factor, also called cachectin), glycine inhibits it. In some situations, glycine is known to suppress the formation of serotonin. Antagonists of serotonin can potentiate glycine's effects(Chesnoy-Marchais, et al., 2000). People who ate traditional diets, besides getting a lower concentration of tryptophan, were getting a large amount of glycine in their gelatin-rich diet.
甘氨酸的多种抗炎和保护作用可以被认为是一种抗血清素的作用。例如,血清素增加TNF(肿瘤坏死因子,也称为cachectin)的形成,甘氨酸则抑制它。在某些情况下,甘氨酸可以抑制血清素的形成。血清素拮抗剂可增强甘氨酸的作用(Chesnoy-Marchais等,2000年)。吃传统饮食的人,除了得到较低浓度的色氨酸,还从富含明胶的饮食中得到大量的甘氨酸。
Gelatin, besides being a good source of glycine, also contains a large amount of proline, which has some antiexcitatory properties similar to glycine.
明胶除了是甘氨酸的良好来源外,还含有大量的脯氨酸,脯氨酸具有与甘氨酸相似的抗兴奋性。
If a half-pound of steak is eaten, it would probably be reasonable to have about 20 grams of gelatin at approximately the same time. Even a higher ratio of gelatin to muscle meat might be preferable.
如果吃了半磅牛排,大约在同一时间摄入大约20克明胶是合理的。甚至更高的明胶与肌肉肉的比例可能是更好的。
Carbon dioxide, high altitude, thyroid, progesterone, caffeine, aspirin, and decreased tryptophan consumption protect against excessive serotonin release. When sodium intake is restricted, there is a sharp increase in serotonin secretion. This accounts for some of the antiinflammatory and diuretic effects of increased sodium consumption–increasing sodium lowers both serotonin and adrenalin.
二氧化碳、高海拔、甲状腺、黄体酮、咖啡因、阿司匹林和色氨酸摄入的减少可以防止过量的血清素释放。当钠摄入量受到限制时,血清素分泌会急剧增加。这就解释了增加钠摄入量的一些抗炎和利尿作用——增加钠摄入量可以降低血清素和肾上腺素。
The polyunsaturated oils interact closely with serotonin and tryptophan, and the short and medium chain saturated fatty acids have antihistamine and antiserotonin actions. Serotonin liberates free fatty acids from the tissues, especially the polyunsaturated fats, and these in turn liberate serotonin from cells such as the platelets, and liberate tryptophan from serum albumin, increasing its uptake and the formation of serotonin in the brain. Saturated fats don't liberate serotonin, and some of them, such as capric acid found in coconut oil, relax blood vessels, while linoleic acid constricts blood vessels and promotes hypertension. Stress, exercise, and darkness, increase the release of free fatty acids, and so promote the liberation of tryptophan and formation of serotonin. Increased serum linoleic acid is specifically associated with serotonin-dependent disorders such as migraine.
多不饱和脂肪酸与血清素和色氨酸相互作用密切,短链和中链饱和脂肪酸具有抗组胺和抗血清素的作用。血清素从组织中释放出游离脂肪酸,尤其是多不饱和脂肪,而这些脂肪酸又从血小板等细胞中释放出血清素,从血清白蛋白中释放出色氨酸,增加了色氨酸的摄取,并促进了大脑中血清素的形成。饱和脂肪不能释放血清素,其中一些,如椰子油中发现的癸酸,可以放松血管,而亚油酸会收缩血管,促进高血压。压力、运动和黑暗,增加了游离脂肪酸的释放,从而促进了色氨酸的释放和血清素的形成。血清亚油酸增加与血清素依赖性疾病如偏头痛有关。
Coconut oil, because of its saturated fatty acids of varied chain length, and its low linoleic acid content, should be considered as part of a protective diet.
椰子油由于其饱和脂肪酸链长不同,亚油酸含量低,应考虑作为保护性饮食的一部分。
In the collagen theory of aging, it is argued that changes in the extracellular matrix are responsible for isolating cells from their environment, reducing the availability of nutrients and oxygen, and reducing their ability to send and receive the chemical signals that are needed for correct adaptive functioning.
衰老的胶原蛋白理论认为,细胞外基质的变化导致细胞脱离环境,减少营养和氧气的可用性,降低细胞发送和接收化学信号的能力,而这些化学信号是正确的适应功能所必需的。
In diabetes, basement membranes are thickened, and in a given volume of tissue there are fewer capillaries. This effect probably involves excessive serotonin(Kasho, et al., 1998). Old animals contain a higher proportion of collagen. Old tendons (or tendons that have been exposed to excessive estrogen, which stimulates the formation of collagen) are more rigid, and behave almost as if they have been partly cooked. In diseases such as carcinoid, in which very large amounts of serotonin are released systemically, fibrosis is exaggerated, and may be the direct cause of death. Radiation and oxygen deprivation also lead to increased tissue fibrosis.
糖尿病患者基底膜增厚,在一定体积的组织中毛细血管较少。这种影响可能涉及过量的血清素(Kasho等,1998)。年老的动物含有更高比例的胶原蛋白。旧的肌腱(或暴露在过量雌激素下的肌腱,刺激胶原蛋白的形成)更硬,表现得几乎就像被部分煮熟了一样。在像类癌这样的疾病中,全身释放大量血清素,纤维化加剧,可能是直接导致死亡的原因。辐射和缺氧也会导致组织纤维化加剧。
In specific fibrotic conditions, such as cirrhosis of the liver, it is known that glycine and saturated fats can reverse the fibrosis. In fibrosis of the heart, thyroid hormone is sometimes able to reverse the condition.
在特定的纤维化情况下,如肝硬化,众所周知甘氨酸和饱和脂肪可以逆转纤维化。在心脏纤维化中,甲状腺激素有时能扭转病情。
I think these facts imply that excessive tryptophan, estrogen, and polyunsaturated fats contribute significantly, maybe decisively, to the degenerative changes that occur in aging. Experiments have separately shown that reducing dietary tryptophan or unsaturated fats can extend the healthy lifespan, and several antiestrogenic interventions (removal of the pituitary, or supplementing with progesterone) can slow age-related changes and delay degenerative diseases. Since these factors interact, each tending to promote the others, and also interact with exogenous toxins, excess iron accumulation, and other stressors, it would be reasonable to expect greater results when several of the problems are corrected at the same time.
我认为这些事实表明,过量的色氨酸、雌激素和多不饱和脂肪对衰老过程中发生的退行性变化起着重要的,也许是决定性的作用。单独的实验表明,减少饮食中的色氨酸或不饱和脂肪可以延长健康的寿命,几种抗雌激素干预(去除脑垂体或补充孕酮)可以延缓与年龄相关的变化和延缓退行性疾病。由于这些因素相互作用,每个因素都倾向于促进其他因素,而且还与外源毒素、过量的铁积累和其他压力源相互作用,因此,当几个问题同时得到纠正时,预期会产生更大的结果是合理的。
http://raypeat.com/articles/aging/tryptophan-serotonin-aging.shtml
REFERENCES
引用
Toxicol Pathol 1998 May-Jun;26(3):395-402. Glycine modulates the toxicity of benzyl acetate in F344 rats. Abdo KM, Wenk ML, Harry GJ, Mahler J, Goehl TJ, Irwin RD. “These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity.”
毒理学杂志1998年5- 6月;26(3):395-402。甘氨酸可调节醋酸苄酯对F344大鼠的毒性。Abdo KM, Wenk ML, Harry GJ, Mahler J, Goehl TJ, Irwin RD.“这些结果表明BA诱导的神经退行性变是由甘氨酸池耗尽和随后的兴奋性毒性介导的。”
Res Clin Stud Headache 1978;6:110-6. Role of individual free fatty acids in migraine. Anthony M “Total plasma free fatty acids, platelet serotonin content and plasma stearic, palmitic, oleic and linoleic acids were estimated in 10 migraine patients before, during and after a migraine attack. Total and individual plasma free fatty acid levels rose and platelet serotonin content fell in most patients. The highest rise was observed in linoleic acid, which is known to be a potent liberator of platelet serotonin in vitro and is the only precursor of all prostaglandins in the body. It is suggested that the rise in plasma levels oflinoleic acid in migraine could be responsible for the platelet serotonin release observed during the attack.”
临床螺柱头痛1978;6:110-6。个体游离脂肪酸在偏头痛中的作用。Anthony M“在10名偏头痛患者偏头痛发作前、期间和之后估计了血浆总游离脂肪酸、血小板血清素含量和血浆硬脂酸、软脂酸、油酸和亚油酸。在大多数患者中,总和个体血浆游离脂肪酸水平升高,血小板血清素含量下降。亚油酸的含量上升幅度最大,亚油酸被认为是体外血小板血清素的有效释放剂,是体内所有前列腺素的唯一前体。这表明,偏头痛患者血浆中亚油酸水平的升高可能与发作期间观察到的血小板血清素释放有关。”
Clin Exp Neurol 1978;15:190-6. Individual free fatty acids and migraine. Anthony M Total plasma free fatty acids (FFAs), platelet serotonin content and plasma stearic, palmitic, oleic and linoleic acids were estimated in 10 migrainous patients before, during and after a migraine attack. Total and individual plasma FFA levels rose and platelet serotonin fell in most patients. Comparison of the pre-headache and headache mean values showed that of the FFAs linoleic acid rises most during headache. 10 non-migrainous controls had platelet serotonin content estimated before and after the ingestion of 20g linoleic acid. All showed a significant fall in platelet serotonin in the post-ingestion period. It is shown that linoleic acid releases platelet serotonin in vitro, and this study suggests that it has the same action in vivo. Further, it is the precursor of all prostaglandins in the body and its marked elevation during migraine may serve as a source of increased prostaglandin E1 (PGE1) synthesis. It is suggested that linoleic acid plays an important role in the biochemical process of the migraine attack, acting both as a serotonin releasing factor and a source of PGF1, the vasodilating action of which can aggravate the clinical symptoms of migraine.
临床实验神经内科1978;15:190-6。个体游离脂肪酸与偏头痛。10名偏头痛患者在偏头痛发作前、期间和之后估计了血浆总游离脂肪酸(FFAs)、血小板血清素含量和血浆硬脂酸、软脂酸、油酸和亚油酸。在大多数患者中,总和个体血浆FFA水平升高,血小板血清素下降。头痛前和头痛平均值的比较表明,FFAs中亚油酸在头痛时上升最多。10名非偏头痛患者在摄入20g亚油酸前后测定了血小板血清素含量。在摄入后的时间里,所有的血小板血清素都显著下降。结果表明,亚油酸在体外释放血小板血清素,本研究提示亚油酸在体内也有同样的作用。此外,它是体内所有前列腺素的前体,偏头痛期间其显著升高可能是前列腺素E1 (PGE1)合成增加的来源。提示亚油酸在偏头痛发作的生化过程中起重要作用,它既是血清素释放因子,又是PGF1的来源,其血管舒张作用可加重偏头痛的临床症状。
J Appl Physiol 1993 Jun;74(6):3006-12. Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. Bailey SP, Davis JM, Ahlborn EN. “Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05).” “Brain 5-HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05).”
应用生理学1993 6月;74(6):3006-12。在长时间运动至疲劳期间,神经内分泌和底物对改变的大脑5-HT活动的反应。Bailey SP, Davis JM, Ahlborn EN。大脑5-羟色胺(5-hydroxytryptamine, 5-HT)活性的药理操纵影响大鼠的奔跑时间至精疲力竭。这些效应可能是由神经化学、激素或基质机制介导的。各组大鼠分别在休息时、在跑步机上跑1小时(20 m/min, 5%等级)后和疲惫时断头。运动前立即腹腔注射二马来酸喹嗪1mg /kg (QD;一种5-HT激动剂),1.5 mg/kg的LY 53857 (LY;5-HT拮抗剂),或车辆(V;0.9%生理盐水)。LY增加了衰竭时间,QD减少了衰竭时间(分别约为28天和32%;P < 0.05)。运动1小时时大脑5-HT和5-羟基吲哚-3-乙酸浓度高于休息时(P < 0.05),疲劳时中脑和纹状体的5-羟吲哚-3-乙酸浓度进一步升高(P < 0.05)。
Neurochem Int 1993 Sep;23(3):269-83. Glutamate, GABA, glycine and taurine modulate serotonin synthesis and release in rostral and caudal rhombencephalic raphe cells in primary cultures.Becquet D, Hery M, Francois-Bellan AM, Giraud P, Deprez P, Faudon M, Fache MP, Hery F.
国际神经化学杂志1993年9月;23(3):269-83。在原代培养中,谷氨酸、GABA、甘氨酸和牛磺酸调节鼻侧和尾侧后脑中缝细胞中血清素的合成和释放。Becquet D, Hery M, Francois-Bellan AM, Giraud P, Deprez P, Faudon M,法希MP, Hery F。
Acta Physiol Scand 2001 Oct;173(2):223-30. Exercise-induced changes in brain glucose and serotonin revealed by microdialysis in rat hippocampus: effect of glucose supplementation. Bequet F, Gomez-Merino D, Berthelot M, Guezennec CY.
物理学报2001 10月;173(2):223-30。运动诱导的大鼠海马葡萄糖和血清素的变化:补充葡萄糖的影响。Bequet F, Gomez-Merino D, Berthelot M, Guezennec CY。
Amino Acids 2001;20(1):25-34. Amino acids and central fatigue. Blomstrand E. “There is an increasing interest in the mechanisms behind central fatigue, particularly in relation to changes in brain monoamine metabolism and the influence of specific amino acids on fatigue.” “When the 5-HT level was elevated in this way the performance was impaired in both rats and human subjects, and in accordance with this a decrease in the 5-HT level caused an improvement in running performance in rats. The precursor of 5-HT is the amino acid tryptophan and the synthesis of 5-HT in the brain is thought to be regulated by the blood supply of free tryptophan in relation to other large neutral amino acids (including the branched-chain amino acids, BCAA) since these compete with tryptophan for transport into the brain.”
氨基酸2001;20(1):25 - 34。氨基酸和中枢疲劳。“人们对中枢疲劳背后的机制越来越感兴趣,特别是与大脑单胺代谢的变化和特定氨基酸对疲劳的影响有关。“当5-HT水平以这种方式升高时,大鼠和人类受试者的运动能力都受到了损害,与此相一致的是,5-HT水平的下降导致了大鼠跑步能力的改善。”5是色氨酸的前体的合成5 -大脑中被认为是由自由色氨酸的血液供应相对于其他大型中性氨基酸(包括支链氨基酸,BCAA)因为这些与色氨酸争夺运输进入大脑。”
J Neurol Sci 1988 Apr;84(2-3):239-46. Increased platelet aggregation and release reaction in myotonic dystrophy. Bornstein NM, Zahavi M, Korczyn AD, Zahavi J.
神经科学杂志1988年4月;84(2-3):239-46。肌强直性营养不良患者血小板聚集和释放反应增加。博恩斯坦,扎哈维M,科尔钦,扎哈维J。
Curr Med Chem 2001 Sep;8(11):1257-74. The inhibitory neural circuitry as target of antiepileptic drugs.Bohme I, Luddens H. “Impairments and defects in the inhibitory neurotransmission in the CNS can contribute to various seizure disorders, i.e., gamma-aminobutyric acid (GABA) and glycine as the main inhibitory neurotransmitters in the brain play a crucial role in some forms of epilepsy.”
Curr Med Chem 2001 Sep;8(11):1257-74。抑制神经回路作为抗癫痫药物的靶点。Bohme I, Luddens H.“中枢神经系统抑制性神经传递的损伤和缺陷可导致各种癫痫疾病,即-氨基丁酸(GABA)和甘氨酸作为大脑中的主要抑制性神经递质,在某些形式的癫痫中发挥关键作用。”
Braz J Med Biol Res 2000 Mar;33(3):355-61. Thyroid peroxidase activity is inhibited by amino acids.Carvalho DP, Ferreira AC, Coelho SM, Moraes JM, Camacho MA, Rosenthal D
医学生物学杂志2000年3月33(3):355-61。甲状腺过氧化物酶活性受到氨基酸的抑制。卡瓦略,费雷拉,科埃略,莫拉莱斯,卡马乔,罗森塔尔
Q J Exp Psychol B 2000 Aug;53(3):225-38. Rapid visual learning in the rat: effects at the 5-HT1a receptor subtype. Cassaday HJ, Simpson EL, Gaffan EA. “The 5-hydroxytryptamine1a (5-HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.15 mg/kg) impaired rats' rapid visual learning on a computerized maze. This treatment also increased decision time (DT) but the learning impairment was not necessarily a side-effect of slower responding because, in this task, responses made at long DT are more accurate than those at short DT.” “Its reversal with WAY-100635 offers support to the hypothesis that 5-HT1a receptor antagonists could improve cognitive function, under conditions of pre-existing impairment due to overactive serotonergic inhibition, as is thought to occur in Alzheimer's disease.”
中国心理学杂志2000年8月;53(3):225-38。大鼠的快速视觉学习:对5-HT1a受体亚型的影响5-羟色胺1a (5-HT1a)受体激动剂8-羟基-2-(二-丙基氨基)四氢萘(8-OH-DPAT;0.15 mg/kg)在电脑迷宫中损害大鼠的快速视觉学习能力。这种治疗也增加了决策时间(DT),但学习障碍不一定是反应慢的副作用,因为在这项任务中,长时间DT作出的反应比短时间DT作出的反应更准确。“WAY-100635的逆转为5-HT1a受体拮抗剂可以改善认知功能的假设提供了支持,这种情况下由于过度活跃的5-羟色胺能抑制已存在的损害,正如人们认为的在阿尔茨海默病中发生的那样。”
Med Sci Sports Exerc 1997 Jan;29(1):58-62. Effects of acute physical exercise on central serotonergic systems. “This paper reviews data concerning the effects of acute physical exercise (treadmill running) in trained rats. Works from the 1980's have established that acute running increases brain serotonin (5-hydroxytryptamine: 5-HT) synthesis in two ways. Lipolysis-elicited release of free fatty acids in the blood compartment displaces the binding of the essential amino acid tryptophan to albumin, thereby increasing the concentration of the so-called “free tryptophan” portion, and because exercise increases the ratio of circulating free tryptophan to the sum of the concentrations of the amino acids that compete with tryptophan for uptake at the blood-brain barrier level, tryptophan enters markedly in the brain compartment. However, this marked increase in central tryptophan levels increases only to a low extent brain 5-HT synthesis, as assessed by the analysis of 5-hydroxyindoleacetic acid levels, thereby suggesting that exercise promotes feedback regulatory mechanisms. Indirect indices of 5-HT functions open the possibility that acute exercise-induced increases in 5-HT biosynthesis are associated with (or lead to) increases in 5-HT release.”
医学体育运动1997 1月;29(1):58-62。急性体育锻炼对中枢5 -羟色胺能系统的影响。“这篇论文综述了关于急性体育锻炼(跑步机跑步)对训练大鼠影响的数据。20世纪80年代的研究已经证实,急性跑步以两种方式增加了大脑血清素(5-羟色胺:5-HT)的合成。脂多糖引起的游离脂肪酸在血腔内的释放取代了必需氨基酸色氨酸与白蛋白的结合,从而增加了所谓的“游离色氨酸”部分的浓度,而且,由于运动增加了循环中的游离色氨酸与在血脑屏障水平上与色氨酸竞争的氨基酸浓度之和的比例,色氨酸显著地进入了脑隔间。然而,通过对5-羟基吲哚乙酸水平的分析评估,中枢色氨酸水平的显著增加仅在较低程度上增加了大脑5-HT合成,因此表明运动促进反馈调节机制。5-HT功能的间接指标开启了一种可能性,即急性运动诱导的5-HT生物合成增加与(或导致)5-HT释放增加有关。”
Int J Dev Neurosci 1997 Apr;15(2):257-63. Postnatal changes of brain monoamine levels in prenatally malnourished and control rats. Chen JC, Turiak G, Galler J, Volicer L.
国际发展神经科学1997年4月15(2):257-63。产前营养不良及对照大鼠产后脑单胺水平的变化。陈家成,图里亚克,加勒,Volicer L。
Eur J Pharmacol 2000 Aug 25;402(3):205-13. Glycinergic potentiation by some 5-HT(3) receptor antagonists: insight into selectivity. Chesnoy-Marchais D, Levi S, Acher F.
Eur J Pharmacol 2000 8月25日;402(3):205-13。一些5-HT(3)受体拮抗剂的甘氨酸能增强作用:对选择性的了解。Chesnoy-Marchais D, Levi S, Acher F。
Mech Ageing Dev 1986 Oct;36(2):161-71. Influence of low tryptophan diet on survival and organ growth in mice. De Marte ML, Enesco HE. Greater survival and reduced growth were found to characterize mice on a tryptophan deficient diet as compared to fully fed control mice. The 50% survival point was reached by the tryptophan restricted group at 683 days, and by the control group at 616 days. Measurements of body weight, organ weight, and DNA level were made at 8, 12, 24, 36, 52 and 78 weeks of age. Both whole body weight and organ weight of liver, kidney, heart and spleen were about 30% lower in the tryptophan restricted group as compared to the controls, so that the ratio of organ weight to body weight remained at a constant value for both groups. There was no significant change in cell number as determined by DNA measurements, as a result of the tryptophan restriction.
机械老化发展1986十月;36(2):161-71。低色氨酸饮食对小鼠生存和器官生长的影响。De Marte ML, Enesco HE。研究发现,与完全喂食色氨酸的对照组小鼠相比,缺乏色氨酸的小鼠存活率更高,生长速度更慢。色氨酸限制组在683 d达到50%的生存点,对照组在616 d达到50%。分别于8、12、24、36、52和78周龄测量体重、器官重量和DNA水平。色氨酸限制组的肝脏、肾脏、心脏和脾脏的全体重量和器官重量均比对照组降低约30%,使两组的器官重量与体重之比保持不变。由于色氨酸限制,DNA测量结果显示细胞数量没有显著变化。
J Clin Psychopharmacol 1999 Dec;19(6):506-12. Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults. File SE, Fluck E, Fernandes C. .”The effects of Bioglycin(Konapharma, Pratteln, Switzerland), a biologically active form of the amino acid glycine, were . . . studied in healthy students (mean age, 20.7 years) and middle-aged men (mean age, 58.9 years) with tests that measured attention, memory and mood, using a double-blind, randomized, crossover design. Compared with the young group, the middle-aged group had significantly poorer verbal episodic memory, focused, divided, and sustained attention; they also differed in their subjective responses at the end of testing. Bioglycin significantly improved retrieval from episodic memory in both the young and the middle-aged groups, but it did not affect focused or divided attention. However, the middle-aged men significantly benefited from Bioglycin in the sustained-attention task. The effects of Bioglycin differed from those of other cognitive enhancers in that it was without stimulant properties or significant effects on mood, and it primarily improved memory rather than attention. It is likely to be of benefit in young or older people in situations where high retrieval of information is needed or when performance is impaired by jet lag, shift work, or disrupted sleep. It may also benefit the impaired retrieval shown in patients with schizophrenia, Parkinson's disease, and Huntington's disease.
临床精神药理学杂志1999年12月;19(6):506-12。甘氨酸(生物甘氨酸)对青壮年人记忆和注意力的有益影响。filse, Fluck E, Fernandes C.“生物霉素(Konapharma, Pratteln, Switzerland)是氨基酸甘氨酸的一种生物活性形式,其作用是…研究对象为健康学生(平均年龄20.7岁)和中年男性(平均年龄58.9岁),采用双盲、随机、交叉设计,对注意力、记忆力和情绪进行测试。与年轻组相比,中年组的言语情景记忆、集中注意力、分裂注意力和持续注意力明显较差;在测试结束时,他们的主观反应也有所不同。在青年和中年组中,生物苷显著改善了情景记忆的提取,但它不影响集中或分散注意力。然而,在持续注意力任务中,中年男性明显受益于生物甘氨酸。生物苷的作用不同于其他认知增强剂,因为它没有兴奋的特性或对情绪的显著影响,它主要是改善记忆力而不是注意力。当年轻人或老年人需要大量的信息检索,或者由于时差、倒班工作或睡眠中断而导致表现受损时,这可能是有益的。它也可能有益于精神分裂症、帕金森病和亨廷顿病患者的恢复功能受损。
Brain Res 1997 Sep 12;768(1-2):43-8. Mobilization of arachidonate and docosahexaenoate by stimulation of the 5-HT2A receptor in rat C6 glioma cells. Garcia MC, Kim HY Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA. “In this study, we demonstrate that astroglial 5-HT2A receptors are linked to the mobilization of polyunsaturated fatty acids (PUFA). Stimulation of C6 glioma cells, prelabeled with [3H]arachidonate (AA, 20:4n6) and [14C]docosahexaenoate (DHA, 22:6n3), with serotonin and the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) resulted in the mobilization of both [3H] and [14C] into the supernatant of the cell monolayers. The increased radioactivity in the supernatant was mainly associated with free fatty acids.” “These results indicate that the 5-HT2A receptor is coupled to the mobilization of PUFA.”
脑研究1997年9月12日;768(1-2):43-8。5-HT2A受体刺激大鼠C6胶质瘤细胞中花生四烯酸和二十二碳六烯酸的活化。国家卫生研究院膜生物化学与生物物理实验室,国家酒精滥用与酒精中毒研究所,罗克维尔,医学博士20852,美国。“在这项研究中,我们证明星形胶质的5-HT2A受体与多不饱和脂肪酸(PUFA)的动员有关。C6神经胶质瘤细胞的刺激,prelabeled [3 h]花生四烯酸(AA, 20:4n6)和[14 c] docosahexaenoate (DHA, 22:6n3)、5 -羟色胺和5 - (2 a / c)受体激动剂(+ / -)2,5-dimethoxy-4-iodoamphetamine盐酸盐(DOI)导致动员[3 h]和[14 c]的浮在表面的细胞层。上清液中放射性增高主要与游离脂肪酸有关。“这些结果表明5-HT2A受体与PUFA的动员是耦合的。”
Neurosci Lett 1995 May 5;190(2):143-5. Serotonin involvement in the spontaneous alternation ability: a behavioral study in tryptophan-restricted rats.Gonzalez-Burgos I, Olvera-Cortes E, Del Angel-Meza AR, Feria-Velasco A. Laboratorio de Psicobiologia, Centro de Investigacion Biomedica de Occidente, IMSS, Guadalajara, Jal., Mexico. Spontaneous alternation (SA) is controlled by septal cholinergic terminals in the hippocampus. Serotoninergic terminals end on cholinergic nerve endings in the hippocampus, and their possible role in SA was investigated in rats fed with a tryptophan-deficient diet, from weaning to 60 days of age. A T-maze was used for the test. At the age of 40 days, an increase in SA occurred in the tryptophan deficient rats, although this effect disappeared by 60 days of age. A modulatory role of serotonin in the psychoneural control of SA is suggested, and it may be through presynaptic inhibition of hippocampal cholinergic terminals.
神经科学Lett 1995 5月5日;190(2):143-5。5 -羟色胺参与自发交替能力:在色氨酸受限大鼠的行为研究。Gonzalez-Burgos I, Olvera-Cortes E, Del Angel-Meza AR, Feria-Velasco A. Laboratorio de psicbiologia, Centro de biomedical de Occidente, IMSS,瓜达拉哈拉,Jal。、墨西哥。自发交替(SA)由海马区间隔胆碱能终末控制。在断奶至60日龄的大鼠中,研究了海马胆碱能神经末梢上的5 -羟色胺能末梢及其在SA中的可能作用。测试使用了t迷宫。在40日龄时,色氨酸缺乏的大鼠的SA增加,尽管这种效应在60日龄时消失。提示5 -羟色胺在SA的精神神经控制中起调节作用,可能是通过突触前抑制海马胆碱能终末。
Physiol Behav 1998 Jan;63(2):165-9. Effect of tryptophan restriction on short-term memory.Gonzalez-Burgos I, Perez-Vega MI, Del Angel-Meza AR, Feria-Velasco A. Centro de Investigacion Biomedica de Michoacan, Instituto Mexicano del Seguro Social, Morelia. Several brain regions are involved in the learning process that is integrated from sensorial inputs. It is thereafter consolidated in short- (STM) or long-term memory. Serotonin is strongly related to both types of memory, and particularly, to STM, however, its regulatory role is still unclear. In this study, the effects of tryptophan (TRY) restriction on learning and STM were evaluated. Ten Sprague-Dawley female rats were fed with a TRY-restricted diet (0.15g/100g) starting from postnatal Day 21. At 21, 40, and 60 days of age, 5 trials per animal were carried out in a “hard-floor”-Biel maze, after 24 h of water abstinence. The number of errors per trial were registered before reachingthe goal. At both 40 and 60 days, experimental rats committed less errors than controls. Likewise, the TRY-restricted group learned the task from the second trial on, whereas controls did not solve it until the third trial. TRY restriction, and therefore brain serotonin reduction, could impair normal cholinergic activity in some areas such as the hippocampus and the cerebral cortex, where involvement in learning and memory is well documented. Morphological and neurochemical plastic events could also be related to the more efficient performance of the task by the TRY-restricted rats.
物理学报1998;63(2):165-9。色氨酸限制对短期记忆的影响。Gonzalez-Burgos I, Perez-Vega MI, Del Angel-Meza AR, Feria-Velasco A. Centro de investigation acion Biomedica de Michoacan, Instituto Mexicano Del Seguro Social, Morelia。有几个大脑区域参与了由感官输入整合而成的学习过程。它随后被巩固为短期(STM)或长期记忆。5 -羟色胺与两种类型的记忆都有密切关系,特别是与STM有关,然而,它的调节作用尚不清楚。本研究评估了色氨酸(TRY)限制对学习和STM的影响。10只雌性sd大鼠从出生后第21天开始饲喂TRY-restricted饲粮(0.15g/100g)。分别在21、40和60日龄断奶24 h后,在“硬地板”-Biel迷宫中进行5次试验。在达到目标之前,每次试验的错误数都被记录下来。在40天和60天,实验大鼠比对照组犯的错误都少。同样,“尝试限制”组在第二次试验时就学会了这个任务,而对照组直到第三次试验时才学会。TRY限制,因此大脑5 -羟色胺减少,可能会损害一些区域的正常胆碱能活动,如海马和大脑皮层,这些区域与学习和记忆有关,这是有充分记录的。形态学和神经化学的可塑性事件也可能与尝试限制的大鼠更有效地完成任务有关。
Am J Physiol 1997 Jul;273(1 Pt 2):R324-30. Mechanisms in the pressor effects of hepatic portal venous fatty acid infusion. Grekin RJ, Dumont CJ, Vollmer AP, Watts SW, Webb RC Portal venous infusion of oleate solution has pressor effects. We have examined efferent mechanisms, measured the response to sustained infusion, and determined the effect of linoleate. Eight conscious animals received concurrent infusions of prazosin or vehicle with portal venous infusion of oleate. Oleate alone increased mean arterial pressure from 109.0 +/- 4.1 to 123.0 +/- 5.8 mmHg (P = 0.02), whereas no increase in blood pressure occurred when oleate was infusedwith prazosin. In 10 rats, concurrent infusion of losartan had no effect on the pressor activity of portal oleate infusion. Twenty-two animals received portal oleate or vehicle as a continuous infusion for 7 days. Mean arterial pressure (126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001) and heart rate (383 +/- 5 vs. 366 +/- 5, P = 0.0257) were increased in oleate-infused animals. No differences in plasma fatty acids, glucose, insulin, pressor hormones, liver enzymes, or in vitro arterial pressor responsiveness were observed. “Portal venous infusion of linoleate increased arterial pressure by 12.2 +/- 3.2 mmHg (P = 0.033). These results indicate that alpha-adrenergic activity is necessary for the acute pressor effects of portal oleate, that sustained portal oleate infusion results in persistent blood pressure elevation, and that other long-chain fatty acids besides oleate have pressor effects.”
美国物理学会1997年7月;273(1 Pt 2):R324-30。肝门静脉脂肪酸输注升压作用的机制。Grekin RJ, Dumont CJ, Vollmer AP, Watts SW, Webb RC门静脉输注油酸溶液有加压作用。我们检查了传出机制,测量了持续输注的反应,并确定了亚油酸的作用。8只意识清醒的动物同时注射吡唑嗪或对照品与门静脉注射油酸盐。油酸单独使平均动脉压从109.0 +/- 4.1增加到123.0 +/- 5.8 mmHg (P = 0.02),而油酸注入吡唑嗪后血压没有增加。在10只大鼠中,同时输注氯沙坦对门脉油酸输注的升压活性无影响。22只动物接受门脉油酸盐或对照品连续输注7天。平均动脉压(126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001)和心率(383 +/- 5 vs. 366 +/- 5, P = 0.0257)增加。在血浆脂肪酸、葡萄糖、胰岛素、加压激素、肝酶和体外动脉加压反应方面没有观察到差异。门静脉输注亚油酸使动脉压升高12.2 +/- 3.2 mmHg (P = 0.033)。这些结果表明-肾上腺素能活动对门脉油酸盐的急性升压作用是必要的,持续门脉油酸盐输注导致持续血压升高,而油酸盐之外的其他长链脂肪酸也有升压作用。”
Adv Exp Med Biol 1999;467:507-16. Tryptophan toxicity–time and dose response in rats. Gross B, Ronen N, Honigman S, Livne E. “During the past decade L-tryptophan (Trp) ingestion have been associated with a multisystemic syndrome, known as eosinophilia myalgia syndrome (EMS). Even though an epidemic studies indicated that a contaminant, 1,1'-ethylidene-bis-L-tryptophan was involved in EMS, abnormalities in metabolism of Trp have been reported in other similar clinical syndromes such as carcinoid syndrome, scleroderma or eosinophilic fasciitis.” “Increased amounts of connective tissue and induction of inflammatory cell proliferation were observed in lung, spleen and in gastrocnemia muscle of rats treated with higher dose of Trp for longer period. Induction of kynurenine pathway by injection of p-CPA caused more tissue damage. It is concluded that excessive Trp or elevation of its metabolites could play a role in amplifying some of pathological features of EMS. This pathological damage is further augmented by metabolites of the kynurenine pathway.”
美国医学杂志1999;467:507-16。色氨酸毒性——大鼠的时间和剂量反应。在过去的十年中,l -色氨酸(Trp)的摄入被认为与多系统综合征有关,即嗜酸性肌痛综合征(EMS)。尽管一项流行研究表明,一种污染物,1,1'-乙基-双l -色氨酸参与了EMS,但在其他类似的临床综合征中,如类癌综合征、硬皮病或嗜酸性筋膜炎,也报道了色氨酸代谢异常。“在大鼠肺、脾和腓肠肌中观察到高剂量色氨酸治疗较长时间后结缔组织增多和炎症细胞增殖的诱导。”通过注射p-CPA诱导犬尿氨酸通路引起更多的组织损伤。由此可见,色氨酸过量或其代谢产物的升高可能会放大EMS的某些病理特征。kynurenine途径的代谢物进一步加剧了这种病理损伤。”
Zh Nevrol Psikhiatr Im S S Korsakova 1999;99(2):12-20. [Neuroprotective effects of glycine in the acute period of ischemic stroke.] [Article in Russian] Gusev EI, Skvortsova VI, Komissarova IA, Dambinova SA, Raevskii KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Iakovleva EV.
科学(d辑:地球科学)1999;99(2):12-20。甘氨酸在缺血性中风急性期的神经保护作用。[俄文]Gusev EI, Skvortsova VI, Komissarova IA, Dambinova SA, Raevskii KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Iakovleva EV。
Pharmacol Biochem Behav 1989 Dec;34(4):823-8. Milacemide, a glycine prodrug, enhances performance of learning tasks in normal and amnestic rodents. Handelmann GE, Nevins ME, Mueller LL, Arnolde SM, Cordi AA. “Increasing glycine concentrations in the brain by administration of a glycine prodrug, milacemide, is shown here to enhance performance of a shock-motivated passive avoidance task in rats, and to reverse drug-induced amnesia in a spontaneous alternation paradigm in mice.” “These studies indicate a role of glycinergic neurotransmission in memory processes, and support the therapeutic potential of glycinergic drugs in memory impairment.”
生物化学学报1989年12月;34(4):823-8。Milacemide,一种甘氨酸前药,提高学习任务的表现在正常和遗忘的啮齿动物。Handelmann GE, Nevins ME, Mueller LL, Arnolde SM, Cordi AA。“通过给甘氨酸前药milacemide增加甘氨酸在大脑中的浓度,在这里显示了在大鼠中增强冲击驱动的被动回避任务的表现,并在小鼠中自发交替范式中逆转药物诱导的遗忘。“这些研究表明了甘氨酸能神经传递在记忆过程中的作用,并支持了甘氨酸能药物在记忆障碍中的治疗潜力。”
Pain 1989 Aug;38(2):145-50. Ketanserin in reflex sympathetic dystrophy. A double-blind placebo controlled cross-over trial. Hanna MH, Peat SJ.
1989年8月,38(2):145 - 50。酮坦色林治疗反射性交感神经营养不良。一项双盲安慰剂对照交叉试验。
Synapse 1997 Sep;27(1):36-44. Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain. Henley WN, Koehnle TJ. “The lack of mechanistic insight reflects, in large part, a longstanding bias that the mature mammalian central nervous system is not an important target site for thyroid hormones.”
突触1997年9月,27(1):36-44。甲状腺激素和抑郁症的治疗:对成熟哺乳动物大脑中基本激素作用的检查。Henley WN, Koehnle TJ。“缺乏机制上的洞察力在很大程度上反映了一种长期存在的偏见,即成熟的哺乳动物中枢神经系统不是甲状腺激素的重要靶点。”
Am J Physiol 1997 Feb;272(2 Pt 2):H894-903. Hypothyroid-induced changes in autonomic control have a central serotonergic component. Henley WN, Vladic F. Three experiments were conducted in unanesthetized rats made hypothyroid (Hypo) or maintained as euthyroid controls (Eu) to examine general cardiovascular responsiveness [experiment I (Exp I)]; responsiveness to a serotonin (5-HT2) agonist, dl-2,5-dimethoxy-4-iodoamphetamine [DOI intracerebroventricularly; experiment II (Exp II)]; or responsiveness to a 5-HT(1A) agonist dl-8-hydroxydipropyl-aminotetralin hydrobromide [8-OH-DPAT intracerebroventricularly; experiment III (Exp III)]. In Exp I, intravenous infusions of phenylephrine and nitroprusside provided little evidence that findings in Exp II and III were caused by generalized impairment in cardiovascular responsiveness in Hypo. In Exp II and III, Eu and Hypo were given either intra-arterial atropine or vehicle. Atropine significantly elevated heart rate (Exp II and III) and mean arterial pressure (Exp II) in Eu only. When compared with Eu, Hypo had a reduced pressor response (5.2 vs. 20.1%), an attenuated pulse pressure response (19.3 vs. 35.4%), and a more robust bradycardia (-17.7 vs. -7.0%) in response to DOI. These differences were atropine sensitive. In Exp III, Hypo had larger decrements in mean arterial pressure (-9.0 vs. -5.1%), heart rate ( -13.9 vs. - 7.7%), and body temperature (-4.5 vs. -2.7%) in response to 8-OH-DPAT in comparison to Eu. Parasympathetic involvement in the differential responses to 8-OH-DPAT was less clear than with DOI. Deranged autonomic control in hypothyroidism may be caused, in part, by changes in central serotonergic activity.
医学杂志1997年2月;272(2 Pt 2):H894-903。甲状腺功能减退引起的自主控制改变具有中枢5 -羟色胺能成分。Henley WN, Vladic F.在未麻醉的甲状腺功能低下(Hypo)或正常对照(Eu)大鼠中进行了三个实验,以检查一般心血管反应[实验I (Exp I)];对5-羟色胺(5-HT2)激动剂dl-2,5-二甲氧基-4-碘安非他命的响应性[脑室内;实验二(实验二);或对5-HT(1A)激动剂dl-8-羟二丙基氨四氢溴化物[8-OH-DPAT脑室内;实验III (Exp III)]。在Exp I中,静脉输注苯肾上腺素和硝普钠的证据很少,证明Exp II和III的发现是由Hypo中心血管反应性的全面性损害引起的。Exp II和III组,Eu和Hypo分别给予阿托品或药物。阿托品显著提高心率(Exp II和III)和平均动脉压(Exp II),仅在欧盟。与Eu相比,Hypo的降压反应降低(5.2 vs. 20.1%),脉压反应减弱(19.3 vs. 35.4%),对DOI有更强的心动过缓(-17.7 vs. -7.0%)。这些差异是阿托品敏感性的。在Exp III中,与Eu相比,Hypo对8-OH-DPAT的平均动脉压(-9.0 vs. -5.1%)、心率(- 13.9 vs. - 7.7%)和体温(-4.5 vs. -2.7%)有更大的下降。副交感神经参与8-OH-DPAT的差异反应不如DOI清楚。甲状腺功能减退患者的自主神经控制紊乱可能部分是由中枢5 -羟色胺能活性的变化引起的。
Brain Res 1986 Mar;390(2):221-6. Brain serotonin synthesis and Na+,K+-ATPase activity are increased postnatally after prenatal administration of L-tryptophan. Hernandez-Rodriguez J, Chagoya G. The effect of prenatal L-tryptophan supplementation on the serotonin (5-HT) synthesis and the activity of Na+,K+-ATPase in the cerebral cortex was studied during postnatal development, from birth up to day 30. A parallel andsignificant elevation of the serotonin content and the activity of tryptophan-5-hydroxylase was observed in the brain of infant rats born to mothers treated with L-tryptophan, as related to non-treated controls. The activity of Na+,K+-ATPase was also significantly elevated at the different ages studied throughout the developmental period, as related to controls. These results suggest an important role of L-tryptophan in the early regulation of the serotonin-synthesizing machinery, which lasts postnatally. Elevation of ATPase activity seems to be associated to the elevation in the activity of the 5-HT system.
科学(d辑:地球科学)1986年3月;产前给予l -色氨酸后,脑5 -羟色胺合成和Na+,K+- atp酶活性增加。研究了产前补充l -色氨酸对产后大脑皮层5-羟色胺(5-HT)合成和Na+,K+- atp酶活性的影响,从出生到30天。与未接受l -色氨酸治疗的对照组相比,经l -色氨酸治疗的母亲所生的幼鼠大脑中血清素含量和色氨酸-5-羟化酶活性有平行和显著的升高。Na+,K+- atp酶的活性在发育的不同时期也显著升高,与对照相关。这些结果表明l -色氨酸在早期5 -羟色胺合成机制的调节中起重要作用,这种调节在产后持续。atp酶活性的升高似乎与5-HT系统活性的升高有关。
Brain Res 1977 Mar 4;123(1):137-45. Daily variations of various parameters of serotonin metabolism in the rat brain. II. Circadian variations in serum and cerebral tryptophan levels: lack of correlation with 5-HT turnover. Hery F, Chouvet G, Kan JP, Pujol JF, Glowinski J “Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues.” “Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels.” “The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum.”
科学(d辑:地球科学);大鼠大脑中血清素代谢的各种参数的日常变化。2血清和大脑色氨酸水平的昼夜变化:与5-HT转换缺乏相关性。Hery F, Chouvet G, Kan JP, Pujol JF, Glowinski J“在大脑组织中发现了5-HT和5-HIAA水平的显著昼夜变化。“游离和总血清色氨酸水平也观察到重要的昼夜变化。”在这两种情况下,在5-HIAA水平峰值后的暗期中期发现了最大水平。“脑组织中色氨酸含量的日变化似乎与血清中色氨酸含量的变化有关。”
Kidney Int 1998 Oct;54(4):1083-92. Serotonin enhances the production of type IV collagen by human mesangial cells. Kasho M, Sakai M, Sasahara T, Anami Y, Matsumura T, Takemura T, Matsuda H, Kobori S, Shichiri M.
国际肝病杂志1998;54(4):1083-92。5 -羟色胺能促进人系膜细胞产生IV型胶原。kaso M, Sakai M, Sasahara T, Anami Y, Matsumura T, Takemura T, Matsuda H, Kobori S, Shichiri M。
Pharmacol Biochem Behav 1977 Sep;7(3):245-52. Fatty acid and tryptophan changes on disturbing groups of rats and caging them singly. Knott PJ, Hutson PH, Curzon G The effects of disturbing groups of 24 hr fasted rats on plasma unesterified fatty acid (UFA) and tryptophan concentrations and brain tryptophan concentrations were investigated. Removing rats from cages rapidly increased plasma UFA and corticosterone and decreased plasma and whole blood tryptophan of cage mates. The disturbance also appeared to influence biochemical values of rats in other cages within the same chamber. Effects specific to individual cages were also suggested. In subsequent experiments 24 fasting rats caged together were rapidly transferred to 24 separate cages and killed at intervals. Plasma UFA rose to a maximum by 12 min and then fell toward initial values. Plasma total tryptophan concurrently fell then rose. Its percentage in the free (ultrafilterable) state, and in some experiments the absolute values of free tryptophan rose then fell. When the latter rise was marked then brain tryptophan and the 5-HT metabolite 5-hydroxyindoleacetic acid rose. Tyrosine changes were negligible. Thus altered brain tryptophan level and 5-HT metabolism may be associated with plasma tryptophan changes caused by brief environmental disturbance.
生物化学学报1977年9月;7(3):245-52。脂肪酸和色氨酸的变化扰乱组大鼠和单独笼子。研究24小时禁食干扰组对大鼠血浆未酯化脂肪酸(UFA)、色氨酸浓度和脑色氨酸浓度的影响。将大鼠从笼中取出后,笼伴血浆不饱和脂肪酸和皮质酮迅速升高,血浆和全血色氨酸降低。这种干扰似乎也影响了同一房间内其他笼子的大鼠的生化值。还提出了个别笼的效应。在随后的实验中,将24只禁食的大鼠关在一起,迅速转移到24个单独的笼子中,每隔一段时间处死。等离子体UFA在12 min时达到最大值,然后向初始值下降。血浆总色氨酸先下降后上升。它在自由(超滤)状态下的百分比,在一些实验中,游离色氨酸的绝对值先上升后下降。当后者明显升高时,大脑色氨酸和5-HT代谢物5-羟基吲哚乙酸升高。酪氨酸变化可以忽略不计。因此,大脑色氨酸水平和5-HT代谢的改变可能与短暂的环境干扰引起的血浆色氨酸变化有关。
J Insect Physiol 2000 May 1;46(5):793-801. Effect of an amino acid on feeding preferences and learning behavior in the honey bee, Apis mellifera. Kim YS, Smith BH. “Subjects preferred to feed on a sucrose stimulus that contained glycine, and the highest relative preference was recorded for the highest concentration of glycine.” “All concentrations of glycine enhanced the rate and magnitude of a conditioned response to an odor . . . .”
昆虫生理学报2000年5月1日;46(5):793-801。一种氨基酸对蜜蜂摄食偏好和学习行为的影响。金泳三,史密斯BH。实验对象更喜欢吃含有甘氨酸的蔗糖刺激物,最高浓度的甘氨酸被记录为最高的相对偏好。“所有浓度的甘氨酸都提高了对气味的条件反应的速率和强度. . . .”
Eur J Pharmacol 1981 May 22;71(4):495-8. Antagonism of L-glycine to seizures induced by L-kynurenine, quinolinic acid and strychnine in mice. Lapin IP.
Eur J Pharmacol 1981 5月22日;71(4):495-8。l -甘氨酸对l -狼氨酸、喹啉酸和士的宁致小鼠癫痫发作的拮抗作用。兔子IP。
Int J Circumpolar Health 1998;57 Suppl 1:386-8. Seasonal variation of the amino acid, L-tryptophan, in interior Alaska. Levine ME, Duffy LK. “The seasonal pattern of L-tryptophan was studied in a Fairbanks, Alaska, population that was unadapted to the extreme light variations of the North. Previously, this population was shown to exhibit seasonal behavior effects such as increases in fatigue and sleep duration, as well as endocrine effects such as increases in melatonin levels and phase shifting.” “Prominent results included finding increased levels in the winter at several different diurnal time points. These findings support hypotheses which relate underlying physiological adaptations to the North to the increased incidence of behavioral disorders such as depression and alcoholism.”
国际极地健康杂志1998;57增刊1:386-8。阿拉斯加内陆氨基酸l -色氨酸的季节变化。Levine ME, Duffy LK“l -色氨酸的季节模式在阿拉斯加费尔班克斯的种群中进行了研究,该种群不适应北方的极端光照变化。此前研究表明,这类人群表现出季节性行为效应,如疲劳和睡眠时间的增加,以及内分泌效应,如褪黑素水平和相位转移的增加。“突出的研究结果包括,在冬季的几个不同的白天时间点发现了浓度的增加。”这些发现支持了以下假设,即北方人潜在的生理适应能力与抑郁症和酗酒等行为障碍发病率的增加有关。”
Infect Immun 2001 Sep;69(9):5883-91. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.
感染免疫2001年9月;69(9):5883-91。膳食甘氨酸可防止大鼠肽聚糖多糖诱导的反应性关节炎:甘氨酸门控氯通道的作用。Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG。
J Neurol Sci 1989 Jan;89(1):27-35. Polyamine biosynthetic decarboxylases in muscles of rats with different experimental myopathies. Lorenzini EC, Colombo B, Ferioli ME, Scalabrino G, Canal N.
神经科学杂志1989,1;89(1):27-35。不同肌病大鼠肌肉中多胺生物合成脱羧酶的研究。Lorenzini EC, Colombo B, Ferioli ME, Scalabrino G, Canal N。
Int J Dev Neurosci 1996 Aug;14(5):641-8. Nutritional recovery does not reverse the activation of brain serotonin synthesis in the ontogenetically malnourished rat. Manjarrez GG, Magdaleno VM, Chagoya G, Hernandez J Coordinacion de Investigacion Biomedica del Centro Medico Nacional, I.M.S.S. Mexico, D.F. In the present work we confirm that gestational malnutrition effects body and brain composition and results in an activation of the synthesis of the brain neurotransmitter 5-hydroxytryptamine. These results also demonstrate more activity of the rate-limiting enzyme tryptophan hydroxylase in the malnourished fetal and postnatal brain. However, the activity of this enzyme remains increased in the brain of nutritionally recovered animals accompanied by an increase in the synthesis of 5-hydroxytryptamine. We therefore suggest that, in the nutritionally recovered animal, the mechanism of activation of this biosynthetic path in the brain may be not dependent on the increased availability of free L-tryptophan observed in malnourished animals, but might be due to a specific change in the enzyme complex itself. This hypothesis is supported by the fact that plasma free and brain L-tryptophan return to normal in the recovered animal.
国际发展神经科学1996 8月;14(5):641-8。营养恢复不会逆转个体遗传营养不良大鼠大脑血清素合成的激活。Manjarrez GG, Magdaleno VM, Chagoya G, Hernandez J coordination de Investigacion de Biomedica del Centro Medico Nacional, I.M.S.S. Mexico, D.F.在目前的工作中,我们证实妊娠营养不良影响身体和大脑的组成,并导致激活脑神经递质5-羟色胺的合成。这些结果也表明,在营养不良的胎儿和出生后的大脑中,限制性酶色氨酸羟化酶的活性更高。然而,在营养恢复的动物的大脑中,这种酶的活性仍然增加,并伴随着5-羟色胺合成的增加。因此,我们认为,在营养恢复的动物中,大脑中这种生物合成途径的激活机制可能并不依赖于营养不良动物中观察到的游离l -色氨酸的增加,而可能是由于酶复合物本身的特定变化。这一假设得到了血浆游离l -色氨酸和大脑l -色氨酸恢复正常的事实的支持。
Brain Res 1997 Nov 7;774(1-2):265-8. Tryptophan ingestion by gestant mothers alters prolactin and luteinizing hormone release in the adult male offspring. Martin L, Rodriguez Diaz M, Santana-Herrera C, Milena A, Santana C.
医学杂志1997年11月7日;774(2):265-8。妊娠母亲摄入色氨酸会改变成年雄性后代泌乳素和促黄体生成素的释放。Martin L, Rodriguez Diaz M, Santana- herrera C, Milena A, Santana C。
Rev Esp Fisiol 1984 Jun;40(2):213-9. [Lipolytic effect of serotonin in vitro]. [Article in Spanish] Martinez-Conde A, Mayor de la Torre P, Tamarit-Torres J The lipolytic action of serotonin on isolated adipocytes from the adipose tissue of rats has been studied. The adipocytes were incubated in serotonin 10(-6) M. Changes both in concentration and composition of the free intra and extracellular fatty acids as well as diacylglycerides through liquid gas chromatography were evaluated at different intervals. A lower concentration of free fatty acids and diacylglycerides is produced during the first minutes of incubation as well as a subsequent increase in the concentration of both, which becomes greatest after 20-30 minutes. The composition of both lipidic fractions (FFA and DAG) into fatty acids at 5, 10, 20 and 30 minutes, is related to the composition of the triacylglycerides (TAG), since during the esterification process a decline in the DAG of linoleic and palmitoleic acid is observed, both acids arranging themselves preferably in the TAG 2 position. Whereas the inverse process occurs during lipolysis; i.e. an increase in the proportion of the acids in the 2 position. In the FFA fraction, a higher proportion of fatty acids, preferential by arranged in positions 1 + 3 of the TAG's is observed. Similarly a decrease is observed in the extracellular concentration of FFA in the presence of serotonin with respect to the controls, a fact which has been described by other authors. An analysis of the present data leads us to revise the possible role of “Cahill's cycle” (simultaneous activation of the DAG-acyl-transferase and the HSL-TAG-lipase) in the action of serotonin and other hormones.
Rev Esp fisisol 1984六月;40(2):213-9。[体外血清素的脂解作用]。研究了5 -羟色胺对大鼠脂肪组织中分离的脂肪细胞的脂解作用。在5 -羟色胺10(-6)m培养液中培养脂肪细胞,通过液相气相色谱法测定细胞内外游离脂肪酸和甘油酯的浓度和组成。在培养的最初几分钟内产生较低浓度的游离脂肪酸和甘油酯,随后这两种脂肪酸的浓度增加,在20-30分钟后达到最大。油脂的分数的组成(FFA和DAG)脂肪酸在5、10、20和30分钟,有关的组成三乙甘油三酯
triacylglycerides(标签),因为在酯化过程中下降DAG亚麻油酸和9 -十六碳烯酸,酸都安排自己最好的标签2的位置。相反的过程发生在脂解过程中;也就是说,2位的酸的比例增加了。在FFA组分中,脂肪酸的比例较高,优先排列在TAG的1 + 3位置。同样,与对照组相比,在血清素存在时,FFA的细胞外浓度也出现了下降,这一事实已被其他作者描述。通过对现有数据的分析,我们修正了“Cahill’s cycle”(同时激活dag -酰基转移酶和hsl - tag -脂肪酶)在血清素和其他激素作用中的可能作用。
Nahrung 1991;35(9):961-7. [The effect of different protein diets on longevity and various biochemical parameters of aged rats]. Medovar BJa, Petzke KJ, Semesko TG, Albrecht V, Grigorov JuG Institut fur Gerontologie, AMW, UdSSR, Kiev. In this work 23 month old rats were fed for 200 days with different protein diets (NT-diet: 19% protein, 72% of animal origin and LP-diet: 8.8% protein exclusively of vegetable origin). Some metabolic parameters and lifespan (on the base of a 50% death-rate) were determined. The relations of the liver free amino acids glycine + alanine and tyrosine + phenylalanine + branched chain amino acids and the ratio of phenylalanine/tyrosine were determined to be higher in the LP-group.Phenylalanine in liver and urea concentrations in liver and serum were lower in the LP-group. Furthermore the dopamine or serotonin levels were significantly lower in lateral and medial or lateral regions of the hypothalamus respectively in LP-diet fed rats. The norepinephrine content was not modified by the diets. The median lifespan of 23 month old rats was higher by 24% following LP-treatment. These results suggest that the protein component (amino acids) of different diets may modify metabolic parameters and lifespan of animals by mechanisms in which the central regulation may be involved.
Nahrung 1991; 35(9): 961 - 7。【不同蛋白质饮食对老龄大鼠寿命及各种生化指标的影响】Medovar BJa, Petzke KJ, Semesko TG, Albrecht V, Grigorov JuG老年研究所,AMW, UdSSR,基辅。23月龄大鼠饲喂不同蛋白质饲料(nt饲料:19%蛋白质,72%来自动物,lp饲料:8.8%纯来自蔬菜)200 d。测定了一些代谢参数和寿命(以50%的死亡率为基础)。肝脏游离氨基酸甘氨酸+丙氨酸和酪氨酸+苯丙氨酸+支链氨基酸的关系及苯丙氨酸/酪氨酸比值在lp组中较高。lp组肝脏中苯丙氨酸、肝脏和血清中尿素浓度均较低。此外,低脂饮食喂养的大鼠下丘脑外侧和内侧或外侧区域的多巴胺或血清素水平均显著降低。去甲肾上腺素含量不受饮食的影响。经过lp治疗后,23个月大鼠的中位寿命提高了24%。这些结果表明,不同饲料中的蛋白质成分(氨基酸)可能通过中枢调控的机制改变动物的代谢参数和寿命。
J Neurol Sci 1976 May;28(1):41-56. Skeletal muscle necrosis following membrane-active drugs plus serotonin. Meltzer HY.
神经科学杂志1976年5月;28(1):41-56膜活性药物加血清素导致骨骼肌坏死。Meltzer HY。
Brain Res Bull 1977 Sep-Oct;2(5):347-53. Effects of developmental protein malnutrition on tryptophan utilization in brain and peripheral tissues. Miller M, Leahy JP, McConville F, Morgane PJ, Resnick O.
2(5):347-53。发育性蛋白质营养不良对大脑和周围组织色氨酸利用的影响。Miller M, Leahy JP, McConville F, morgan PJ, Resnick O。
Exp Neurol 1977 Oct;57(1):142-57. Tryptophan availability: relation to elevated brain serotonin in developmentally protein-malnourished rats. Miller M, Leahy JP, Stern WC, Morgane PJ, Resnick O.
神经科学,色氨酸可用性:与发育性蛋白质营养不良大鼠大脑血清素升高的关系。Miller M, Leahy JP, Stern WC, morgan PJ, Resnick O。
Synapse 1990;6(4):338-43. Age-related changes of strychnine-insensitive glycine receptors in rat brain as studied by in vitro autoradiography. Miyoshi R, Kito S, Doudou N, Nomoto T. “3H-glycine binding sites were most concentrated in the hippocampus, cerebral cortex, and olfactory tubercle, and moderate densities of binding sites were located in the striatum, nucleus accumbens, amygdala, and certain thalamic nuclei.” “In aged animals, severe decline of 3H-glycine binding sites was observed in the telencephalic regions including the hippocampus and cerebral cortex.” “These results suggest that the decrease of glycine receptors in particular brain regions has some relation with changes of neuronal functions associated with aging process in these areas.”
突触1990;6(4):338 - 43。体外放射自显影研究大鼠脑中士的九不敏感甘氨酸受体的年龄相关性变化。Miyoshi R、Kito S、Doudou N、Nomoto T.”3h -甘氨酸结合位点主要集中在海马、大脑皮层和嗅觉结节,中等密度的结合位点分布在纹状体、伏隔核、杏仁核和某些丘脑核。“在老年动物中,海马和大脑皮层等端脑区域的3h -甘氨酸结合位点严重下降。“这些结果表明,大脑特定区域甘氨酸受体的减少与这些区域中与衰老过程相关的神经元功能的变化有一定的关系。”
Enzyme 1976;21(6):481-7. Inhibition of actomyosin ATPase by high concentrations of 5-hydroxytryptamine. Possible basis of lesion in 5HT-induced experimental myopathy. Mothersill C, Heffron JJ, McLoughlin JV.
酶1976;21(6):481 - 7。高浓度5-羟色胺对肌动球蛋白atp酶的抑制作用。5ht诱导的实验性肌病病变的可能基础。Mothersill C, Heffron JJ, McLoughlin JV。
Brain Res 1975 Jul 25;93(1):123-32. Regulation of 5-hydroxytryptamine metabolism in mouse brain by adrenal glucocorticoids. Neckers L, Sze PY “A single injection of hydrocortisone acetate (HCA; 20 mg/kg, i.p.) accelerated the accumulation of 5-HT in whole brain after inhibition of monoamine oxidase activity by paragyline. The hormone did not appear to change brain tryptophan hydroxylase or 5-hydroxytryptophan decarboxylase activity. However, tryptophan levels in brain were elevated by 50% within 1 h after treatment with HCA.”
脑研究1975年7月25日;93(1):123-32。肾上腺糖皮质激素对小鼠脑内5-羟色胺代谢的调节。醋酸氢化可的松(HCA;20 mg/kg, i.p。)通过抑制单胺氧化酶活性,可加速全脑5-HT的积累。这种激素似乎没有改变大脑色氨酸羟化酶或5-羟基色氨酸脱羧酶的活性。然而,大脑中的色氨酸水平在使用HCA治疗后1小时内升高了50%。”
Proc Soc Exp Biol Med 1967 Nov;126(2):579-83. Serotonin antagonist increases longevity in mice with hereditary muscular dystrophy. O'Steen WK.
生物医学杂志1967年11月126(2):579-83。5 -羟色胺拮抗剂可增加遗传性肌营养不良小鼠的寿命。
Mech Ageing Dev 1988 Apr;43(1):79-98. Histology and survival in age-delayed low-tryptophan-fed rats. Ooka H, Segall PE, Timiras PS. Diets containing tryptophan in concentrations 30 and 40 percent of those fed to controls from weaning to 24-30 months or more, can delay aging in Long-Evans female rats. Mortality among low-tryptophan-fed rats was greater in the juvenile period, but substantially less than controls at late ages. Histological biomarkers of aging were also delayed after tryptophan restriction in some organs (liver, heart, uterus, ovary, adrenal and spleen) but not in others (kidney, lung, aorta). Brain serotonin levels were low in tryptophan-deficient rats but showed remarkable capacity for rehabilitation. Effects on early and late mortality and brain levels of serotonin were proportional to the severity of the restriction.
机械老化发展1988年4月;43(1):79-98。迟发性低色氨酸喂养大鼠的组织学和生存。从断奶到24-30个月或更长时间,色氨酸浓度为对照组的30%和40%的饮食可以延缓长伊万斯雌性大鼠的衰老。低色氨酸喂养的大鼠在幼年期的死亡率更高,但在后期明显低于对照组。在一些器官(肝脏、心脏、子宫、卵巢、肾上腺和脾脏)限制色氨酸后,衰老的组织学生物标志物也会延迟,但在其他器官(肾脏、肺、主动脉)则不会。色氨酸缺乏的大鼠大脑血清素水平较低,但表现出显著的康复能力。对早期和晚期死亡率和大脑血清素水平的影响与限制的严重程度成正比。
Age Ageing 1985 Mar;14(2):71-5. Plasma tryptophan, age and depression. Phipps DA, Powell C. Plasma, obtained from 131 nondepressed, otherwise healthy subjects aged from 17 to 102 years, and 22 depressed subjects aged over 70 years, was analysed for total and free tryptophan. Variation with age was found in total tryptophan. This association has not been described hitherto. There was a significant increase in total tryptophan and a non-significant increase in free tryptophan with depression. This is in contrast to some studies in younger people showing a decline in plasma tryptophan in depressed subjects.
年龄老龄化1985年3月14(2):71-5。血浆色氨酸、年龄和抑郁症。Phipps DA, Powell C.从年龄在17 - 102岁之间的131名非抑郁的健康受试者和22名年龄在70岁以上的抑郁受试者的血浆中分析了总色氨酸和游离色氨酸。总色氨酸随年龄变化。这种联系迄今尚未被描述过。抑郁症患者总色氨酸显著增加而游离色氨酸无显著增加。这与一些在年轻人中进行的研究形成了对比,这些研究显示抑郁症患者的血浆色氨酸水平下降。
Bratisl Lek Listy 1975 Jul;64(1):58-63. [The effect of serotonin on the release of free fatty acids from human and rat adipose tissue (author's transl)].[Article in Czech] Rath R, Kujalova V.
Bratisl Lek Listy 1975 7月;64(1):58-63。[血清素对人体和大鼠脂肪组织释放游离脂肪酸的影响(作者翻译)]。[捷克文]Rath R, Kujalova V。
Adv Exp Med Biol 1999;467:497-505. Oxidative damage in rat tissue following excessive L-tryptophan and atherogenic diets. Ronen N, Livne E, Gross B.
美国医学杂志1999;467:497-505。过量l -色氨酸和致动脉粥样硬化饮食对大鼠组织氧化损伤的影响。Ronen N, Livne E, Gross B。
FASEB J 1994 Dec;8(15):1302-7. Methionine restriction increases blood glutathione and longevity in F344 rats. Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA “Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001).”
科学(d辑:地球科学)1994年12月;8(15):1302-7。蛋氨酸限制可增加F344大鼠的血谷胱甘肽水平和寿命。Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA“与对照组相比,Met限制导致平均寿命增加42%,最大寿命增加44%,体重降低43% (P < 0.001)。在成熟和老年met限制动物中,血液谷胱甘肽水平分别增加81%和164% (P < 0.001)。”
Carcinogenesis 1999 Nov;20(11):2075-81. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Rose ML, Cattley RC, Dunn C, Wong V, Li X, Thurman RG.
致癌作用1999;11月20(11):2075 - 81。食用甘氨酸可防止过氧化物酶体增殖物wy - 14643引起的肝脏肿瘤的发生。Rose ML, catley RC, Dunn C, Wong V, Li X, Thurman RG。
Mech Ageing Dev 1983 Nov-Dec; 23(3-4):245-52. Low tryptophan diets delay reproductive aging. Segall PE, Timiras PS, Walton JR. Newly weaned female rats fed diets severely deficient in the essential amino acid tryptophan show marked delays in reproductive aging, with conception and delivery occurring as late as 36 months. The rate of aging in these rats seems inversely related to both their early growth rates and the accessibility of brain tryptophan. The subsequent age retardation may depend on a reduction in both early cell loss and rate of brain maturation.
Mech Ageing Dev 1983 11 - 12月;23日(3 - 4):245 - 52。低色氨酸饮食可以延缓生殖衰老。饲喂严重缺乏必需氨基酸色氨酸的饲料的刚断奶的雌性大鼠生殖衰老明显延迟,怀孕和分娩迟至36个月。这些老鼠的衰老速度似乎与它们的早期生长速度和大脑色氨酸的可及性呈负相关。随后的年龄迟缓可能取决于早期细胞丧失的减少和大脑成熟的速度。
Mech Ageing Dev 1978 Jan;7(1):1-17. Neural and endocrine development after chronic tryptophan deficiency in rats: I. Brain monoamine and pituitary responses. Segall PE, Ooka H, Rose K, Timiras PS. “Caloric restriction and tryptophan deficient diets have been shown to delay aging in the immature laboratory rat.” “Another group of animals, in which growth and maturation was delayed by feeding d,1-parachlorophenylalanine (PCPA) showed decreases in serotonin, norepinephrine and dopamine concentrations in all brain regions investigated. All treatments employed to arrest growth and maturation resulted in pituitary alterations manifested by gross, histological and ultrastructural changes. It is postulated that there maturation- and age-retarding treatments delay the development of the central nervous system resulting in postponed maturation of the neuroendocrine axis, with consequent hypoactivity of certain pituitary functions and a resultant delay in the onset of maturation and senescence.”
机械老化发展1978年1月;7(1):1-17。大鼠慢性色氨酸缺乏后神经和内分泌发育:I.脑单胺和垂体反应。西格尔PE, Ooka H, Rose K, Timiras PS.“热量限制和色氨酸缺乏的饮食已经被证明可以延缓不成熟的实验室大鼠的衰老。“另一组动物的生长和成熟被喂食d,1-对氯苯丙氨酸(PCPA)显示血清素,去甲肾上腺素和多巴胺浓度在所有被调查的大脑区域下降。”所有用于阻止生长和成熟的治疗导致垂体的改变,表现为肉眼、组织学和超微结构的改变。据推测,成熟和衰老延缓治疗延迟了中枢神经系统的发育,导致神经内分泌轴的延迟成熟,从而导致某些垂体功能的活性低下,并导致成熟和衰老的开始延迟。”
Aktuelle Gerontol 1977 Oct;7(10):535-8. Long-term tryptophan restriction and aging in the rat. Segall P. Growth-retarded rats fed a tryptophan deficient diet at 21 days for periods of 6-22 months were shown to reach normal body weight when subsequently fed Purina Rat Chow. They demonstrated an increased ability over similar aged controls to recover from hypothermia induced by 3-minute whole-body ice water immersion, were able to bear litters at 17–28 months of age, showed a delay in the age of onset of visible tumors, and indicated an increase in their average lifespan at late ages. Animals fed on this diet from 3 months of age revealed a similar ability to reproduce at advanced ages, but not as marked as those placed on the diet earlier. The average lifespan (in months +/- the standard error of the mean) of the rats recovering from the long-term tryptophan-deficient diets was 36.31 +/- 2.26 while the control rats survived an average of 30.5 +/- 1.90 months. The last of 8 rats surviving the period of tryptophan-deficiency died at 45.50 months (1387 days) while the last of 14 control rats died at 41.75 months (1266 days). It is hypothesized that some kind of subtle mechanism exerts its influence on the rats during the period of tryptophan deficiency which caused an accelerated morbidity and mortality as they approached senescence approximately 1 to 2 years after refeeding. This is parallel to the situation with immature animals subjected to long-term caloric restriction and then fed on normal diets.
Aktuelle Gerontol 1977 Oct;7(10):535-8。长期的色氨酸限制和大鼠的衰老。生长发育迟缓的大鼠在6-22个月期间,在第21天喂食色氨酸缺乏的饲料,随后喂食Purina鼠粮,结果显示大鼠达到正常体重。他们在相似年龄的能力有所增强控制恢复体温过低引起的3分钟全身冰水浸泡,能忍受窝在17 - 28个月的年龄,表现出时代的延迟出现可见的肿瘤,并表示他们的平均寿命的增加在末时代。从3个月大开始吃这种食物的动物在年老时显示出类似的繁殖能力,但没有那些更早吃这种食物的动物表现得那么明显。从长期色氨酸缺乏饮食中恢复的大鼠的平均寿命(月+/-平均值的标准误差)为36.31 +/- 2.26,而对照组大鼠的平均寿命为30.5 +/- 1.90个月。色氨酸缺乏期存活的8只大鼠最后死亡45.50个月(1387天),对照组14只大鼠最后死亡41.75个月(1266天)。推测是某种微妙的机制在色氨酸缺乏症期间对大鼠产生影响,在进食后约1 ~ 2年接近衰老时,色氨酸缺乏症会加速大鼠的发病率和死亡率。这与未成熟的动物长期受到热量限制,然后以正常饮食喂养的情况类似。
Mech Ageing Dev 1976 Mar-Apr;5(2):109-24. Patho-physiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging. Segall PE, Timiras PS. Long-Evans female rats three weeks, three months and 13-14 months of age were placed on tryptophan-deficient diets for periods ranging from a few months to nearly two years. Growth was interupted during the period of tryptophan-deficiency, but when the animals were returned to a complete diet, they gained weight and grew to normal size. Ability to reproduce, as indicated by litter production, was present at 17-28 months of age in rats which had been deprived of tryptophan, whereas no controls over 17 months of age produced any offspring. Other signs of delayed aging in the experimental group included, at advanced ages, greater longevity, as well as later onset in the appearance of obvious tumors, and better coat condition and hair regrowth. Many of these effects were also seen in pair-fed controls (fed a diet equal in amount to that eaten by the tryptophan-deprived rats, but with 1-tryptophan added). It is hypothesized that tryptophan deficiency delays growth, development and maturation of the central nervous system (CNS), in particular, by decreasing the levels of the neurotransmitter serotonin, for which tryptophan is the necessary precursor. In a parallel experiment, chronic treatment with d, 1-parachlorophenylalanine, an inhibitor of brain serotonin synthesis, from weaning until adulthood, also inhibited growth (body weight) and delayed sexual maturation (age of vaginal opening). These observations suggest that diets deficient in tryptophan or restricted in calories can affect maturation and aging by interfering with CNS protein synthesis, or neurotransmitter metabolism, or both.
机械老化发展1976年3 - 4月;5(2):109-24。大鼠慢性色氨酸缺乏后的病理生理学发现:一种延迟生长和衰老的模型。长埃文斯(Long-Evans)雌性大鼠分别为3周、3个月和13-14个月大,饲喂色氨酸缺乏的食物,喂养期从几个月到两岁不等。在色氨酸缺乏期间,生长被中断,但当动物恢复完全的饮食后,它们的体重增加,体形恢复正常。被剥夺色氨酸的老鼠在17-28个月大的时候就有繁殖能力,而对照组在17个月大的时候没有产生任何后代。实验组中延迟衰老的其他迹象包括,年龄大,寿命长,明显肿瘤出现的时间晚,以及更好的皮毛状况和毛发再生。这些效果在成对喂食的对照组中也能看到(喂食的食物与缺乏色氨酸的老鼠的食物数量相同,但添加了1-色氨酸)。假设色氨酸缺乏可以通过降低神经递质血清素的水平来延缓中枢神经系统(CNS)的生长、发育和成熟,而血清素是神经递质血清素的必要前体。在一项平行实验中,从断奶到成年,用d, 1-对氯苯丙氨酸(一种大脑血清素合成抑制剂)长期治疗,也抑制生长(体重)和延迟性成熟(阴道开放年龄)。这些观察表明,缺乏色氨酸或限制热量的饮食可以通过干扰中枢神经系统蛋白质合成或神经递质代谢,或两者兼而有之,从而影响成熟和衰老。
Naturwissenschaften 1965 Sep;52(18):519. [Serotonin-caused muscular dystrophy]. [Article in German] Selye H.
《1965年9月,52(18):519。(Serotonin-caused肌肉萎缩症)。[德文]
Toxicology 1999 Feb 15;132(2-3):139-46. Protection against chronic cadmium toxicity by glycine. Shaikh ZA, Tang W
毒理学1999年2月15日;132(2-3):139-46。防止甘氨酸对镉的慢性毒性。
Biosci Biotechnol Biochem 1998 Mar;62(3):580-3. Increased conversion ratio of tryptophan to niacin in severe food restriction. Shibata K, Kondo T, Miki A.
生物技术与生物化学1998年3月;62(3):580-3。在严格的食物限制下色氨酸与烟酸的转换比率增加。
Monogr Neural Sci 1976;3:94-101. Sex, migraine and serotonin interrelationships. Sicuteri F, Del Bene E, Fonda C. “Sexual deficiency or frank impotence in man could be due to an imbalance of monoamines, particularly 5-HT, at the mating center level. An absolute or relative excess of 5-HT seems to antagonize testosterone at the level of the mating center receptors in the brain. Plasma testosterone levels in so-called psychological impotence are normal. When the 5-HT concentration in sexually deficient men is sufficiently decreased with parachlorophenylalanine (PCPA) treatment and testosterone levels increased following its administration, a vivid sexual stimulation appears in about half of the untractable cases.” “Yet the PCPA-MAOI treatment avoids the prostate carcinogenic risk of testosterone administration in aging males, and seems to have euphorizing effects stronger than those expected only from MAOI therapy. Because of the several side effects of PCPA-MAOI testosterone, the present experiments should be interpreted very cautiously.”
神经科学1976;3:94-101。性、偏头痛和血清素的相互关系。男性的性缺陷或阳痿可能是由于单胺,特别是5-HT,在交配中心水平的不平衡。5-HT的绝对或相对过量似乎能拮抗大脑中交配中心受体水平上的睾丸激素。所谓的心理性阳痿的血浆睾酮水平是正常的。当对氯苯丙氨酸(PCPA)治疗使性缺陷男性的5-HT浓度充分降低,而睾酮水平在其治疗后增加时,约半数难以处理的病例出现生动的性刺激。“然而,PCPA-MAOI疗法避免了老年男性服用睾酮导致的前列腺癌风险,而且似乎有比仅使用MAOI疗法更强的愉悦效果。”由于PCPA-MAOI睾酮的几种副作用,目前的实验应该非常谨慎地解释。”
Hepatology 1999 Mar;29(3):737-45. Glycine and uridine prevent D-galactosamine hepatotoxicity in the rat: role of Kupffer cells. Stachlewitz RF, Seabra V, Bradford B, Bradham CA, Rusyn I, Germolec D, Thurman RG.
肝脏病学1999年3月,29(3):737 - 45。甘氨酸和尿苷预防大鼠d -半乳糖胺肝毒性:库普弗细胞的作用。Stachlewitz RF, Seabra V, Bradford B, Bradham CA, Rusyn I, Germolec D, Thurman RG。
Eur J Appl Physiol Occup Physiol 1999 Mar;79(4):318-24. Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets. Struder HK, Hollmann W, Platen P, Wostmann R, Weicker H, Molderings GJ. “The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress.” “The present results support the hypothesis that acute endurance exercise may increase 5-HT availability. This was reflected in the periphery by increased concentration of the 5-HT precursor free TRP, by increased plasma PRL concentration, and by a reduction of 5-HT2A receptors on platelets.”
欧洲应用生理学和职业生理学1999年3月79(4):318-24。急性和慢性运动对人血小板血浆氨基酸和催乳素浓度及[3H]酮坦色林与血清素2a受体结合的影响Struder HK, Hollmann W, Platen P, Wostmann R, Weicker H, Molderings GJ。神经递质血清素(5-羟色胺,5-HT)已经被证明可以调节各种生理和心理功能,比如疲劳。改变5 -羟色胺能系统的调节已被认为在应对运动压力中发挥作用。“目前的结果支持了这样的假设,即急性耐力运动可能增加5-HT的可用性。”这反映在外周血5-HT前体游离色氨酸浓度增加,血浆PRL浓度增加,血小板上5-HT2A受体减少。”
Epilepsy Res 1999 Jan;33(1):11-21. Pharmacokinetic analysis and anticonvulsant activity of glycine and glycinamide derivatives. Sussan S, Dagan A, Bialer M.
癫痫研究1999年1月33(1):11-21。甘氨酸和甘氨酸酰胺衍生物的药代动力学分析和抗惊厥活性。susan S, Dagan A, Bialer M。
Adv Biochem Psychopharmacol 1976; 15:251-65. Glucocorticoid regulation of the serotonergic system of the brain. Sze PY. “Glucorticoids at concentrations above 10(-7) M stimulate the uptake of tryptophan by brain synaptosomes.”
Adv Biochem Psychopharmacol 1976;15:251 - 65。糖皮质激素对大脑5 -羟色胺能系统的调节。Sze PY。浓度在10(-7)M以上的糖皮质激素刺激大脑突触体吸收色氨酸。
Neurobiol Aging 1984 Fall;5(3):235-42. Lifetime brain serotonin: regional effects of age and precursor availability. Timiras PS, Hudson DB, Segall PE. “In the rat, regional brain serotonin levels which do not change from 2-30 months of age are increased at 36 months.” “Impaired brain serotonin levels recover moderately but remain lower than controls as late as 36 months, growth is never completely compensated, and norepinephrine levels show a rebound increase.”
神经生物学杂志;5(3):235-42。终身脑血清素:年龄和前体可用性的区域效应。Timiras PS, Hudson DB, segal PE。“在大鼠身上,大脑区域血清素水平在2-30个月时没有变化,但在36个月时增加了。“受损的大脑血清素水平会适度恢复,但直到36个月后仍低于对照组,生长从未完全得到补偿,去甲肾上腺素水平出现反弹上升。”
Kidney Int 1996 Feb;49(2):449-60. Cytoprotection of kidney epithelial cells by compounds that target amino acid gated chloride channels. Venkatachalam MA, Weinberg JM, Patel Y, Saikumar P, Dong Z
国际肾脏杂志1996年2月;49(2):449-60。靶向氨基酸门控氯离子通道的化合物对肾脏上皮细胞的保护作用。
Am J Physiol Lung Cell Mol Physiol 2000 Aug;279(2):L390-8. Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Wheeler MD, Rose ML, Yamashima S, Enomoto N, Seabra V, Madren J, Thurman RG.
Am J Physiol Lung Cell Mol Physiol 2000 Aug;279(2):L390-8。食源性甘氨酸可钝化急性内毒素引起的肺部炎症细胞内流。Wheeler MD, Rose ML, Yamashima S, Enomoto N, Seabra V, Madren J, Thurman RG。
Am J Physiol 1999 Nov;277(5 Pt 1):L952-9. Production of superoxide and TNF-alpha from alveolar macrophages is blunted by glycine. Wheeler MD, Thurman RG.
美国物理杂志1999年11月;277(5 Pt 1):L952-9。由肺泡巨噬细胞产生的超氧化物和tnf -被甘氨酸钝化。惠勒医学博士,瑟曼RG。
Stroke 1991 Apr;22(4):469-76. Identification of capric acid as a potent vasorelaxant of human basilar arteries. White RP, Ricca GF, el-Bauomy AM, Robertson JT “To determine whether naturally occurring fatty acids, especially saturated ones, might act directly as vasodilators, segments of human basilar arteries and umbilical arteries were precontracted submaximally with prostaglandin F2 alpha and then exposed to different saturated fatty acids (C4 through C16) or unsaturated fatty acids (C14:1, C18:1, C18:2, and C18:3) at concentrations from 4 microM to 4 mM. The results showed caprate (C10) to be the most potent vasorelaxant and basilar arteries to be more responsive (EC50 = 63 microM) than umbilical arteries (EC50 = 780 microM). Caprate also inhibited contractions elicited by KCl, serotonin, and the thromboxane analogue U46619.”
中风1991年4月,22(4):469 - 76。癸酸作为人基底动脉强效血管松弛剂的鉴定。“为了确定自然产生的脂肪酸,特别是饱和脂肪酸,是否可能直接作为血管扩张剂,将人基底动脉和脐动脉部分以前列腺素F2 α预收缩,然后暴露于不同的饱和脂肪酸(C4至C16)或不饱和脂肪酸(C14:1, C18:1, C18:2,结果显示,caprate (C10)是最有效的血管松弛剂,基底动脉的反应(EC50 = 63 microM)比脐动脉(EC50 = 780 microM)更强。Caprate还能抑制由KCl、血清素和血栓素类似物U46619引起的收缩。”
Neurochem Res 1978 Jun;3(3):295-311. Adaptive changes induced by high altitude in the development of brain monoamine enzymes. Vaccari A, Brotman S, Cimino J, Timiras PS.
神经化学学报1978;3(3):295-311。高海拔诱发脑单胺酶发育的适应性变化。Vaccari A, Brotman S, Cimino J, Timiras PS。
Growth Dev Aging 1991 Winter; 55(4):275-83. Effect of aging and diet restriction on monoamines and amino acids in cerebral cortex of Fischer-344 rats.Yeung JM, Friedman E.
1991年冬季生长发育老龄化;55(4): 275 - 83。衰老和限制饮食对fisher -344大鼠大脑皮质单胺和氨基酸的影响。
Proc Natl Acad Sci U S A 1992 Jul 15;89(14):6443-6. Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids. Yoshida K, Asaoka Y, Nishizuka Y “Several cis-unsaturated fatty acids such as oleic, linoleic, linolenic, eicosapentaenoic, and docosahexaenoic acids added directly to intact human platelets greatly enhance protein kinase C activation as judged by the phosphorylation of its specific endogenous substrate, a 47-kDa protein.” “In the presence of ionomycin and either 1,2-dioctanoylglycerol or phorbol 12-myristate 13-acetate, the release of serotonin from the platelets is also remarkably increased by cis-unsaturated fatty acids. The effect of these fatty acids is observed at concentrations less than 50 microM. Saturated fatty acids and trans-unsaturated fatty acids are inactive.” “. . . cis-unsaturated fatty acids increase an apparent sensitivity of the platelet response to Ca2+. The results suggest that cis-unsaturated fatty acids, which are presumably produced from phosphatidylcholine by signal-dependent activation of phospholipase A2, may take part directly in cell signaling through the protein kinase C pathway.”
美国国立科学研究院1992年7月15日;89(14):6443-6。二酰基甘油和不饱和脂肪酸同时激活血小板。吉田K, Asaoka Y, Nishizuka Y”等cis-unsaturated脂肪酸油的,亚麻油酸、亚麻酸、二十碳五烯,和二十二碳六烯酸直接添加完整的人类血小板大大增强蛋白激酶C的激活根据其特定的内源性底物磷酸化,47-kDa蛋白质。“在有离子霉素、1,2-二辛酰甘油或佛波尔12-肉豆酸13-乙酸酯存在的情况下,顺式不饱和脂肪酸也显著增加了血小板中血清素的释放。”这些脂肪酸的作用是在浓度小于50微米时观察到的。饱和脂肪酸和反式不饱和脂肪酸是不活性的。“……”顺式不饱和脂肪酸增加血小板对Ca2+反应的表观敏感性。结果表明,顺式不饱和脂肪酸可能通过蛋白激酶C途径直接参与细胞信号传导。顺式不饱和脂肪酸可能是磷脂酰胆碱通过磷脂酶A2的信号依赖激活而产生的。
Jpn J Physiol 1969 Apr 15;19(2):176-86. Lipolytic action of serotonin in brown adipose tissue in vitro.Yoshimura K, Hiroshige T, Itoh S
医学杂志1969年4月15日;19(2):176-86。5 -羟色胺在棕色脂肪组织中的脂解作用。yoshiura K, Hiroshige T, Itoh S
Hepatology 2000 Sep;32(3):542-6. Glycine prevents apoptosis of rat sinusoidal endothelial cells caused by deprivation of vascular endothelial growth factor. Zhang Y, Ikejima K, Honda H, Kitamura T, Takei Y, Sato N
肝脏病学2000年9月,32(3):542 - 6。甘氨酸可防止血管内皮生长因子剥夺引起的大鼠窦状内皮细胞凋亡。
Mol Pharmacol 1999 Sep;56(3):455-63. Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney.Zhong Z, Connor HD, Yin M, Moss N, Mason RP, Bunzendahl H, Forman DT, Thurman RG
医药科学1999年9月;56(3):455-63。膳食甘氨酸和肾去神经抑制环孢素a诱导的大鼠肾脏羟基自由基生成。Zhong Z, Connor HD, Yin M, Moss N, Mason RP, Bunzendahl H, Forman DT, Thurman RG