Effect Of Tryptophan Administration Research Articles

The effect of tryptophan administration on the circadian rhythms of melatonin in plasma and the pineal gland of rats

Summary The most physiological processes that take place in the body have a circadian rhythm which is controlled by an internal biological clock located in the suprachiasmatic nucleus. The indole melatonin synthesized in the pineal gland, acts to synchronize these biological rhythms, and also it is synthesized and released following a circadian rhythm. The present study analyzed the levels of melatonin over a 24-hour period in Wistar rats in both basal and control conditions and after the oral administration of 125 mg/kg tryptophan, the amino acid that is the precursor of this indole, for 7 days. The levels of melatonin in the plasma and the pineal gland were measured by radioimmunoassay every hour during the night, and every 4 hours during the day. The results indicated that the tryptophan administration provoked raised levels of melatonin at all hours studied in both plasma and pineal. Of the chronobiological parameters studied, there were also increases in the values of the melatonin MESOR with respect to the values obtained in the basal and control groups (the respective increases being 45% and 52% in plasma, and 46% and 47% in the pineal), as well as an advanced acrophase with respect to the basal and control groups. In summary, our findings confirm that tryptophan intake one hour before lights-off increases melatonin levels in plasma and pineal over a 24-hour period, as well as advancing the peak of its synthesis.

The effect of tryptophan administration on ileum contractility and oxidant status in mice

L-tryptophan (TRP) is the precursor amino acid for the synthesis of serotonin (5-HT). 5-HT is effective both on the food intake and gastrointestinal system contractility. The aim of this study was to search the effects of systemic TRP treatment on 5-HT levels of ileum and searching the effect of ileal contractility and oxidant status. Swiss-albino mice were divided into two groups: 1. Control, 2. TRP-treated (100 mg/kg/24 h, i.p., for 7 days). Body weights were recorded at the beginning and at the end of experiments. Acetylcholine-induced contractile responses in the isolated ileum were recorded on polygraph. Ileal tissue malondialdehyde and glutathione levels determined by spectrophotometric and ileal tissue 5-HT levels were measured by immunohistochemical methods. TRP treatment decreased body weight and increased ileal contractile response. In the TRP-treated group, ileum malondialdehyde levels increased and glutathione levels decreased. Immunohistochemical detection showed that ileal 5-HT levels were increased by TRP treatment. There is a relationship between increased oxidative stress and increased contractility in the ileal tissue of the TRP-treated animals. These effects may be related to increased ileal 5-HT synthesis.

Effect of tryptophan administration on circulating levels of melatonin and phagocytic activity

Our research group has previously studied the role of melatonin in the immune system of birds and mice, finding that incubation with both pharmacological and physiological doses of melatonin augmented the activity of phagocytes from these animals, and that this activity was lowered in pinealectomized animals. Since melatonin is synthesized from the amino acid tryptophan, the aim of the present work was to determine whether the administration of tryptophan might affect the plasma levels of melatonin and the phagocytic activity of peritoneal macrophages over the course of a circadian cycle. The study animals were 14-week-old male Wistar rats. They were administered tryptophan orally in a daily single dose of 125 mg/kg at 19:00 h for 21 days. Prior to beginning this treatment, the circadian rhythms of plasma melatonin and phagocytic activity were evaluated under basal conditions over a 24-h period, taking blood and cell suspension samples each 2 hours during the light period (08:00-20:00) and each hour during the dark period (20:00-08:00), since it is during this latter period that the secretion of melatonin is maximum. The results showed that, under basal conditions, the rats' plasma melatonin levels and phagocytic activity peaked at 02:00. After the tryptophan administration, there were increases in plasma melatonin levels with respect to basal and control-group values, with a peak at 21:00, and in the phagocytic activity of the peritoneal macrophages, which peaked at 02:00. This suggests that the tryptophan administration stimulated melatonin synthesis, leading to increased and earlier peaking plasma levels of this hormone, and augmented the innate immune response carried out by the peritoneal macrophages as a result of the immunoregulatory action of melatonin.

Tryptophan administration increase contractility and change the ultrastructure of mice duodenum

Serotonin (5-HT) is a metabolite of tryptophan (TRP). 5-HT has been shown to induce contractions in rat duodenum and ileum. We planned to investigate the in vivo effects of TRP administration on duodenal contractility and ultrastructure together. Two equal groups of adult male Swiss-albino mice were used in the experiments. Controls (CONT) and TRP treated (100 mg/kg/24 hr in 0.2 ml. saline solution ip, 7 days). Body weights were recorded at the beginning and at the end of experiments. Duodenum tissues contractility responses to different concentration of KCl and acethycholine (ACh) were recorded on polygraph. The ultrastructural changes in duodenum observed by transmission electron microscopic (TEM) method and 5-HT levels determined by immunohistochemical method. Body weights decreased and duodenal contractile response of ACh increased significantly by TRP treatment. The duodenal ultrastructural changes in TRP group illustrated partially loss of apical surface and fusion in microvilli. Immunohistochemical detection showed that 5-HT increased by TRP treatment. There is a relation between duodenal contractility increased by TRP treatment and changes in the duodenal tissue 5-HT level and ultrastructure.

Effect of tryptophan administration on circulating melatonin levels in chicks and rats: Evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract

The administration of L-tryptophan (Trp, 150–300 mg/kg) to rats and chicks causes a rapid and dose-dependent elevation of circulating melatonin. The elevation of serum melatonin was greater after oral compared to the intraperitoneal route of administration of the same dose of Trp (150 mg/kg). The Trp-induced increase of circulating melatonin was unaffected by prior pinealectomy but was almost abolished by a partial ligature of the portal vein. The Trp-induced increase of melatonin in the portal blood preceded that in the systemic circulation. The gut contains considerable amounts of melatonin and the Trp-induced elevation of melatonin was greater in the duodenum compared to the pineal or the blood. The enterochromaffine cells of the gastrointestinal tract appear to be the major source of the Trp-induced increment of circulating melatonin. The possibility is discussed that the sedating, sleep inducing effects of Trp are mediated by the Trp-induced elevation of circulating melatonin.

Effects of tryptophan administration on tetrahydrobiopterin level in rat caudate nucleus

Effects of acute and chronic 1-tryptophan (1-Trp) administrations on caudate biopterin and indoleamine levels were examined in the present study. Results indicate that 1-Trp markedly elevated biopterin, tryptophan, serotonin and 5-hydroxyindoleacetic acid concentrations 2 h after an acute systemic injection. The same effects were not observed 8 and 16 h later. On the contrary, 1-Trp administration via s.c. implanted osmotic minipumps for 24 h and 7 day significantly decreased biopterin content in the caudate nucleus. Serum biopterin level was markedly decreased following 24 h 1-Trp flow and gradually returned to the control levels at 7 day. These results suggest that 1-Trp may have different mechanisms in regulating the activity of tetrahydrobiopterin, the reduced form of biopterin, in the brain and the serum. For short-term regulation, 1-Trp may change the coupling between tryptophan hydroxylase and quinonoid dihydropterin reductase; for long-term regulation, more complicated mechanisms such as substrate and/or product inhibition of enzyme activity may be involved.

Exogenous Tryptophan Increases Synthesis, Storage, and Intraneuronal Metabolism of 5‐Hydroxytryptamine in the Rat Hypothalamus

The effects of tryptophan administration on neurochemical estimates of synthesis [5-hydroxytryptophan (5-HTP) accumulation following administration of a decarboxylase inhibitor], storage [5-hydroxytryptamine (5-HT) concentrations], and metabolism [5-hydroxyindoleacetic acid (5-HIAA) concentrations] of 5-HT in selected regions of the hypothalamus were determined using HPLC coupled to an electrochemical detector. Tryptophan methyl ester HCl (30-300 mg/kg i.p.) produced a dose-dependent increase in the rate of 5-HTP accumulation throughout the hypothalamus but had no effect on the rate of accumulation of 3,4-dihydroxyphenylalanine. Peak 5-HTP levels were attained by 30 min following administration of tryptophan (100 mg/kg i.p.) and were maintained for an additional 60 min. Tryptophan also produced concomitant dose-dependent increases in 5-HT and 5-HIAA concentrations in these same regions without changes in the 5-HIAA/5-HT ratio. These results indicate that exogenous tryptophan administration selectively increases the synthesis, storage, and metabolism of 5-HT in the hypothalamus without altering the synthesis of catecholamines. Inhibition of 5-HT uptake with chlorimipramine or fluoxetine produced modest (10-40%) reductions in 5-HIAA concentrations throughout the hypothalamus, revealing that only a minor portion of 5-HIAA is derived from released and recaptured 5-HT, whereas the major portion of this metabolite reflects intraneuronal metabolism of unreleased 5-HT. In both chlorimipramine- and fluoxetine-treated rats, 5-HIAA concentrations were significantly increased by tryptophan administration, indicating that the increase in synthesis of 5-HT following precursor loading is accompanied by an increase in the intraneuronal metabolism of 5-HT.

Effect of tryptophan administration on spontaneous and p-CPA-induced muricidal aggression in laboratory rats

Summary Muricidal activity, by which some strains of rats stereotypically kill mice, can be induced in laboratory rats by surgical, pharmacological or environmental manipulations, which consistently impair serotonergic transmission in the brain of treated animals in a variety of ways. Manipulations of tryptophan intake result in either facilitation or reduction of spontaneous muricidal activity in rats. In this framework, p-CPA inducesmuricidal activity in naive laboratory rats, even against any genetic predisposition, and orally-administered 1-tryptophan is shown to inhibit p-CPA-induced muricidal aggression.

Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.

Tryptophan 5-hydroxyindoleacetic acid and indoleacetic acid were measured in cerebrospinal fluid taken during pneumoencephalography from patients, some of whom took a 3 g or 6 g tryptophan load at various times before. Measurements were made on both lumbar and cisternal cerebrospinal fluid and the results showed similarities between indoleamine metabolism in human brain and spinal cord. Our data suggested that (1) the blood-brain barrier active transport system for tryptophan is not far from saturation with tryptophan and the rate-limiting enzyme in 5-hydroxytryptamine (5HT) synthesis, tryptophan hydroxylase, is about half saturated. Therefore, both 3 g and 6 g tryptophan loads produced the same maximum rise in 5HT synthesis of just under 100%, (2) tryptamine differs from 5HT in two respects. It is more sensitive to changes in tryptophan availability than 5HT and the 6 g load increased brain tryptamine metabolism more than the 3 g load; also some of the tryptamine in brain is derived from peripheral sources and diffuses from blood to brain, (3) although the brain tryptamine content is much lower than that of 5HT, its rate of metabolism as indicated by CSF metabolite levels is not. In controls the rate of tryptamine metabolism is 15% of the rate of 5HT metabolism and this can increase to 40% after a 6 g tryptophan load.

Effect of tryptophan administration on serotonin and 5-hydroxyindoleacetic acid content in the brainstem of Lilly 110140-pretreated rats

Adult male Sprague-Dawley rats were divided into 3 groups. One group was pretreated with Lilly 110140 (10 mg/kg) 27 hours and again 3 hours before sacrifice while a second group received Lilly 110140 only 3 hours before sacrifice. The third or control group received only equivalent volumes of saline. Animals from each group were administered 25 mg/kg L tryptophan intraperitoneally (i.p.) 0, 30, 60 or 90 minutes before sacrifice. Equivalent elevations in serum and also brainstem tryptophan content were observed in all three groups with the peak observed at 30 minutes. Brainstem serotonin content was significantly elevated in both groups of Lilly 110140-pretreated rats but not in the control group. Brainstem 5-hydroxyindoleacetic acid was significantly elevated after tryptophan administration in the control and the 3 hour and 27 hour, Lilly 110140-pretreated groups but not in the 3 hour Lilly 110140 pretreated group. The results indicate that neither 3 or 3 hours and 27 hours of Lilly 110140 pretreatment appreciably affects the increase in brainstem serotonin synthesis induced by the i.p. administration of 25 mg/kg of L tryptophan.

The Effect of Tryptophan Administration on Fatty Acid Synthesis in the Livers of Rats under Various Nutritional Conditions<xref ref-type="fn" rid="fn1"><sup>1</sup></xref>

1. Tryptophan was administered to rats under various nutritional conditions: fasted for 24 hr, fasted and refed with glucose or corn-oil, fasted and administered glycerol intramuscularly, and nonfasted. 2. The changes in the contents of glycolytic intermediates in the livers indicated that the phosphoenolpyruvate carboxykinase [EC 4.1.1.32] reaction is inhibited by tryptophan administration in all groups of rats. The inversely related changes in the contents of malate and phosphoenolpyruvate were associated with the accumulation of quinolinate in the livers. The content of quinolinate which exhibited the half-maximal effect on the contents of both metabolites was 0.1-0.2 mumole per g liver. 3. The rate of incorporation of 3H from 3H2O into the total hepatic fatty acids was increased about 2-fold by the administration of this amino acid to the fasted rats. The enhancement of the rate was closely related to the increase in the citrate content. The hyperlipogenesis was also related to the decrease of acetyl-CoA and the increase of malonyl-CoA. The content of long-chain acyl-CoA was not affected. These effects of tryptophan administration on the hepatic fatty acid metabolism were found in all groups of rats. The liver content of glycerol 3-phosphate was decreased by tryptophan administration was markedly increased by glycerol injection. The injection of glycerol into the control and the tryptophan-treated rats produced a marked increase of glycerol 3-phosphate but did not affect the rate of fatty acid synthesis in the livers of either group. 4. It may be concluded that, in the livers of rats under various nutritional conditions, the short-term control of fatty acid synthesis by tryptophan administration is most likely due to the activation of acetyl-coenzyme A carboxylase [EC 6.4.1.2] by citrate.

The effect of tryptophan administration on fatty acid synthesis in the liver of the fasted normal rat

1. 1. Tryptophan was administered to the fasted normal rats. The rates of the incorporation of radioactivities from tritiated water and [1- 14C]acetate into hepatic fatty acids in vivo were enhanced about 2-fold by the treatment. 2. 2. Contents of intermediates in relation to the changes in carbohydrate and fatty acid metabolisms were determined. 3. 3. The rate of hepatic fatty acid synthesis was closely related to the content of citrate in the tissue. 4. 4. Hepatic pyruvate dehydrogenase was converted into an inactive form by tryptophan administration. The level of the activity of the enzyme was found to be related to the increase in fatty acid synthesis and accumulation of intermediates of the tricarboxylic acid cycle.

5-Hydroxytryptamine metabolism in affective illness: the effect of tryptophan administration.

SYNOPSISL-tryptophan 50 mg/kg was administered orally to patients suffering from either unipolar or bipolar affective illness, and the concentration of 5-hydroxyindol-acetic acid estimated in their cerebrospinal fluid eight hours later. There was no significant difference between the patient groups or between these and patients with neurological disease. These findings suggest a reduced neuronal activity in the 5-hydroxytryptaminergic system in some depressed patients rather than an absolute deficiency of tryptophan-5-hydroxylase. The synthesis of 5-HIAA in response to tryptophan varied with age.

Interaction in the cerebral metabolism of the biogenic amines: effect of intravenous infusion of L-tryptophan on tryptophan and tyrosine in brain and body fluids.

1. The distribution of the amino-acids tryptophan and tyrosine has been determined in plasma ultrafiltrate, whole plasma, erythrocytes, cerebrospinal fluid (c.s.f.) and various regions of the brain in dogs.2. The effect of tryptophan administration on the distribution of both these amino-acids showed that the alterations produced in tryptophan concentration did not appear to change the concentrations of tyrosine from their normal pattern.3. The implications of these results with regard to amino-acid transport systems in man and dog are discussed.

Effect of tryptophan administration on 5HIAA in cerebrospinal fluid in man.

Effect of tryptophan administration on 5HIAA in cerebrospinal fluid in man.