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Evidence for the absorption and synthesis of 5-hydroxytryptamine in perfused muscle and intestinal tissue and whole worms of adult Ascaris suum.

The metabolites of 5-hydroxytryptamine (5-HT, serotonin) namely, L-tryptophan, 5-hydroxytryptophan, 5-hydroxyindole acetic acid and 5-hydroxytryptophol were measured in perfused tissue and whole worms from adult female Ascaris suum using reversed-phase liquid chromatography with electrochemical detection. The intracellular levels of each metabolite were quantitated in response to several physiological effectors but only L-tryptophan (TRP) caused dose-dependent changes in these metabolites. Serotonin itself could also be absorbed by perfused A. suum muscle and intestinal tissue. When live A. suum were tied at the anterior and posterior regions to restrict TRP absorption by the intestine, TRP was absorbed through the cuticle and converted into 5-HT by the muscle tissue. In united live parasites TRP absorption was observed in both muscle and intestinal tissue. Collectively, the data indicated that 5-HT may be either absorbed directly or synthesized de novo from absorbed TRP in the isolated tissue of A. suum. The 5-HT, in the adult female A. suum, can be synthesized de novo from TRP, or 5-HT can be absorbed from the environment both through the cuticle and by the intestine of living parasites. Data also indicated that there was preferential sequestering of 5-HT and the metabolites of 5-HT in the anterior tissues of the worms.

5-Hydroxytryptophan↗

Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin.

Alcohols and aldehydes in the metabolic pathways of ethanol and serotonin are substrates for alcohol dehydrogenases (ADH) of class I and II. In addition to the reversible alcohol oxidation/aldehyde reduction, these enzymes catalyse aldehyde oxidation. Class-I gammagamma ADH catalyses the dismutation of both acetaldehyde and 5-hydroxyindole-3-acetaldehyde (5-HIAL) into their corresponding alcohols and carboxylic acids. The turnover of acetaldehyde dismutation is high (kcat = 180 min-1) but saturation is reached first at high concentrations (Km = 30 mm) while dismutation of 5-HIAL is saturated at lower concentrations and is thereby more efficient (Km = 150 microm; kcat = 40 min-1). In a system where NAD+ is regenerated, the oxidation of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid proceeds with concentration levels of the intermediary 5-HIAL expected for a two-step oxidation. Butanal and 5-HIAL oxidation is also observed for class-I ADH in the presence of NADH. The class-II enzyme is less efficient in aldehyde oxidation, and the ethanol-oxidation activity of this enzyme is competitively inhibited by acetate (Ki = 12 mm) and 5-hydroxyindole-3-acetic acid (Ki = 2 mm). Reduction of 5-HIAL is efficiently catalysed by class-I gammagamma ADH (kcat = 400 min-1; Km = 33 microm) in the presence of NADH. This indicates that the increased 5-hydroxytryptophol/5-hydroxyindole-3-acetic acid ratio observed after ethanol intake may be due to the increased NADH/NAD+ ratio on the class-I ADH.

Alcohol Dehydrogenase↗

Prevalence of high alcohol and benzodiazepine consumption in sleep apnea patients studied with blood and urine tests.

OBJECTIVE: To evaluate the prevalence of alcoholism and benzodiazepine abuse among patients with obstructive sleep apnea syndrome (OSAS). Such abuse may aggravate the tendency to apneas, especially in patients with OSAS. MATERIAL AND METHODS: The study included 98 consecutive OSAS patients. Two patients dropped out; blood samples could not be obtained from two other patients and a urine sample could not be obtained from one. Blood and urine samples were examined for carbohydrate-deficient transferrin (CDT) and 5-hydroxytryptophol (5-HTOL), markers of excess alcohol intake, and urine-benzodiazepines (u-Benz), a marker of drug abuse. Patients with positive screening tests were offered therapy for their abuse. RESULTS: The CDT test was positive in 8/94 patients (8.5%), the 5-HTOL test in 6/95 (6.3%) and the u-Benz test in 3/95 (3.2%). CONCLUSIONS: Our findings correlate well with current views concerning alcohol and drug abuse in Sweden, and do not indicate that the frequency of such abuse is higher among OSAS patients. It should be noted that none of the patients who screened positive in the laboratory tests admitted to being alcohol or drug abusers when they consulted their physician. We recommend screening all OSAS patients for alcohol abuse using not only a questionnaire but also a laboratory test such as the CDT test.

Adult↗

Sub-populations of alcohol-dependent patients: differences in psychological functioning between high- and low-frequency alcohol consumers.

The purpose of the present study was to examine the processes underlying relapse to drinking using objective biological validation of self-reported recent alcohol consumption, using the ratio of 5-hydroxytryptophol to 5-hydroxyindol-3-ylacetic acid (5-HTOL/5-HIAA), a new biological marker to detect single episodes of drinking, in a sample of 38 male alcohol-dependent patients (DSM-III-R) who were assessed prospectively in terms of their clinical symptomatology over a 6-month treatment period. Results showed that nearly all patients obtained positive 5-HTOL/5-HIAA samples during the course of treatment. However, upon closer inspection, results revealed a bimodal distribution for alcohol intake with high and low frequency of consumption episodes. Results showed that high frequency consumers obtained higher ratings of clinical symptoms as measured by the Comprehensive Psychopathological Rating Scale (CPRS) and by the St Göran's Semi-structured Interview (SGSI) compared to low frequency alcohol consumers on symptoms of inner tension, lack of initiative, risk of relapse (as rated by therapists and as rated by patients themselves), dysphoria, negative craving for alcohol, and positive craving for alcohol. The present results provided evidence for the existence of two sub-populations of alcoholics, those who have frequent lapses and those who have low frequency of sporadic lapses. Further, these two sub-populations were shown to differ with respect to overall psychological functioning, and craving for alcohol. In conclusion, the present findings have important treatment implications in that reliable identification of patients' consumption patterns using biological markers would allow for the design of individually tailored treatment needs.

Adaptation, Psychological↗

Evidence for an endogenous clock in the retina of rainbow trout: II. Circadian rhythmicity of serotonin metabolism.

The purpose of the present study was to investigate patterns of circadian rhythmicity in the retina of a salmonid fish, the rainbow trout (Oncorhynchus mykiss). Our data present the first demonstration of intraretinal variations of serotonergic substances under light/dark-conditions (LD) and during continuous darkness (DD). All substances examined (serotonin, N-acetyl serotonin, 5-hydroxytryptophol, 5-hydroxyindole acetic acid) were rhythmic in LD. Serotonin, N-acetyl-serotonin, and 5-hydroxyindole acetic acid showed a preservation of specific features of rhythmicity in DD indicating the involvement of an endogenous pacemaker in the regulation of serotonin metabolism in the rainbow trout eye.

Animals↗

Detection of relapses in alcohol-dependent patients using carbohydrate-deficient transferrin: improvement with individualized reference levels during long-term monitoring.

The present study examined whether the sensitivity of carbohydrate-deficient transferrin (CDT) in serum, a biochemical marker of recent excessive alcohol consumption, could be improved during long-term monitoring by introducing individualized cut-offs between normal and elevated CDT levels. Alcohol-dependent male outpatients (n = 22), trying to abstain from alcohol for 6 months, were monitored by comparing weekly measurements of CDT with self-reports of alcohol consumption three times/week and daily urinary levels of 5-hydroxytryptophol (5-HTOL), a new marker of recent alcohol intake. The method used to calculate cut-offs was based on the intraindividual variation in CDT not dependent on excessive alcohol consumption or analytical variations. An increase in CDT exceeding the minimum level for each patient by 3 and 4 times the mean coefficient of variation for healthy social drinkers (i.e., by 30% and 40%) was compared as an indication of alcohol consumption, even if the value did not exceed the conventional cut-off. By using individualized CDT cut-off points, 68 and 41 episodes of drinking were detected in the patients with the cut-offs of > 30% and > 40%, respectively, as compared with 25 with the conventional limit. Most episodes could be verified clinically and/or by elevated urinary 5-HTOL levels during the 2-week period preceding each serum sampling. The results suggest that the possibility to detect relapses by CDT can be improved during long-term monitoring of alcohol-dependent outpatients by introducing individualized cut-off points between normal and elevated CDT levels.

Adult↗

The ethanol conjugate ethyl glucuronide is a useful marker of recent alcohol consumption.

BACKGROUND: Current biological state markers remain suboptimal with regard to sensitivity and specificity for monitoring alcohol consumption. The currently used state markers can be influenced by age, sex, and a variety of substances and non-alcohol-associated diseases and do not fully cover the time axis for alcohol intake. Ethyl glucuronide (EtG) is a promising, nonvolatile, water-soluble marker of recent alcohol consumption that is stable during storage and can be detected for an extended time period (up to 80 hr) after alcohol is completely eliminated from the body. PATIENTS AND METHODS: In the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence, EtG was determined in urine samples from 304 patients with an liquid chromotography, electrospray ionization double mass spectrometry (ESI-LC/MS-MS) method. Deuterium labeled EtG was used as internal standard. Determination limit was 0.1 mg/liter. All measurements were performed in duplicate. A calibration solution was measured after each 10 samples. RESULTS: The following significant correlations were found for the Spearman rank correlation for the total sample between EtG and other variables: sobriety in days (r = -0.6), 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid (HTOL/HIAA) ratio (r = 0.58), ethanol level (r = 0.433), methanol level (r = 0.198), carbohydrate-deficient transferrin (r = 0.458), gamma-glutamyltransferase (r = 0.428), aspartate aminotransferase (r = 0.260), age (r = 0.264), and total grams of ethanol consumed in the previous month (r = 0.467). In a subsample of 277 subjects in whom no ethanol was detectable in urine, the following correlations with EtG levels were found: sobriety (days; r = -0.597), HTOL/HIAA ratio (r = 0.478), gamma-glutamyltransferase (r = 0.422), total grams of ethanol consumed last month (r = 0.395), and carbohydrate-deficient transferrin (r = 0.366; all significant at p < 0.05). When we compared results between EtG levels and the HTOL/HIAA ratio, 68.8% (n = 119) of those positive for EtG did not have elevated values for the HTOL/HIAA ratio. Thirty-one percent (31.2%) of these 119 subjects were positive for both parameters, but of those negative for EtG, only 4.4% had an elevated HTOL/HIAA ratio. CONCLUSIONS: EtG is a good candidate for a sensitive, specific, and reliable marker of recent alcohol intake. The complementary use of this marker with other biological state markers should significantly improve treatment outcome and therapy effectiveness and reduce costs.

Adolescent↗

Electrical responses of pineal cells to pineal indoles and putative transmitters in intact and blinded pigeons.

The effects of micro-electrophoretically applied pineal indoles, melatonin (MEL), 5-methoxytryptophol (MTL) and 5-hydroxytryptophol (HTL) and of the neurotransmitters, noradrenaline (NOR), acetylcholine (ACH) and gamma-aminobutyric acid (GABA) on the electrical activity of pineal cells were studied in anaesthetized pigeons. Recordings were made from both sighted and blinded birds during both the day- and night-time. Both excitatory and inhibitory responses to the application of all substances tested were observed, while in all cases unresponsive cells were also found. The pattern of responses to MEL, MTL and to NOR varied significantly depending on whether the cells in the sighted pigeons were tested during the day or at night. This day/night rhythm of responses to MEL and to MTL also occurred in the blinded pigeons, although this was not the case for the effects of NOR. Units which were orthodromically excited by electrical stimulation of the habenular complex were also excited by application of GABA. The activity of these units was also likely to be enhanced by application of ACH. The results suggest that the pigeon pineal organ exhibits intrinsic circadian rhythmicity which does not require entrainment signals from the retina. They also indicate that the activity of pineal cells could be influenced by neurotransmitter input provided from within the gland or via its innervation.

Acetylcholine↗

Effect of indolamines on beta-endorphin release by rat anterior pituitary cells.

The effect of indolamine derivatives on beta-endorphin (beta-end) release has been studied in vitro using rat anterior pituitary cells. Incubation of primary cultures for 2 h with 100 nmol/l of melatonin, serotonin or 5-methoxytryptamine significantly increased the beta-end release in response to 20 nmol/l of ovine corticotropin-releasing factor (oCRF). Incubation of the cultures with 100 nmol/l of L-tryptophan, 5-hydroxy-L-tryptophan, 5-hydroxytryptophol or 5-methoxytryptophol had no effect on basal or CRF-induced beta-end release. The effect of serotonin and melatonin was further tested in a superfusion system of dispersed rat anterior pituitary cells. Superfusion with oCRF (200 nmol/l) for 4 min elicited an immediate rapid increase in beta-end release which lasted 30-40 min. Simultaneous superfusion with melatonin (1 mumol/l) or serotonin (1 mumol/l) significantly increased the effect of oCRF pulses on beta-end release. We conclude that melatonin and serotonin are able to act directly on anterior pituitary cells to potentiate the effect of oCRF on beta-end release.

5-Hydroxytryptophan↗

Vascular responsiveness to serotonin metabolites in mineralocorticoid hypertension.

This study characterizes vascular responsiveness to serotonin and its metabolites and to several monoamines that are structurally related to serotonin in deoxycorticosterone acetate (DOCA)-salt hypertension. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. Dose-response curves to serotonin in arteries from hypertensive rats were shifted significantly to the left compared with those in arteries from normotensive rats (ED25: DOCA-treated = 2.4 X 10(-8) M; control = 17.1 X 10(-8) M). Contractile responses to 5-hydroxyindole acetic acid and 5-hydroxytryptophol were greater in mesenteric arteries from hypertensive rats, whereas reactivity to 5-methoxytryptamine and melatonin in arteries from hypertensive rats did not differ from that in arteries from normotensive rats. Mesenteric arteries from both rat groups were unresponsive to the serotonin metabolite N-acetylserotonin. Contractile responses to 5,6-dihydroxytryptamine and 6-hydroxytryptamine were greater in mesenteric arteries from hypertensive rats, whereas responsiveness to 3-hydroxytryptamine in hypertensive arteries did not differ from normotensive values. Contractile responses to serotonin and its metabolites and to the structurally related monoamines were inhibited by the serotonergic antagonist ketanserin. These results demonstrate that vascular sensitivity to serotonin is increased in DOCA-hypertensive rats. Based on the experiments with serotonin metabolites and with other monoamines, the increased responsiveness to these compounds appears to be related to the structural location of hydroxyl and amine moieties.

5,6-Dihydroxytryptamine↗

Biochemical detection and monitoring of alcohol abuse and abstinence.

The merits and limitations of traditional and new markers for alcohol abuse (and abstinence) are critically examined for detection and monitoring of alcoholics, hazardous drinkers and binge drinkers. The traditional markers discussed include gamma-glutamyltransferase (GGT), aspartate and alanine aminotransaminases (AST, ALT) and mean corpuscular volume (MCV); new markers include mitochondrial AST, carbohydrate-deficient transferrin (CDT), serum/urine 5-hydroxytryptophol, beta-hexosaminidase and acetaldehyde adducts. The strengths and weaknesses of several of the self-reporting screening questionnaires are also explored. No laboratory test is reliable enough on its own to support a diagnosis of alcoholism. Sensitivities and specificities vary considerably and depend on the population concerned. GGT continues to remain the test that combines greatest convenience and sensitivity: its diagnostic accuracy can be enhanced by combination with other traditional markers (AST, ALT, MCV). None of the newer markers offers significant advantage, although CDT seems to be better at monitoring patients for increased alcohol consumption or progress towards abstinence.

Acetaldehyde↗

Changes in rodent thyroid hormones and cyclic-AMP following treatment with pineal indolic compounds.

Treatment of rats with pineal indolic compounds 5-methoxytryptophol, 5-hydroxytryptophol and serotonin brought about a significant increase in serum thyroxine levels, while serotonin and melatonin caused an increase in thyroid cAMP content with corresponding decrease in the gland's hormones. The total quantity of cAMP in the thyroid was also increased by melatonin in the organ culture system. All these findings would indicate that some of the pineal indoleamines elicit a direct action on the thyroid by stimulating the adenyl cyclase activity and intrathyroidal cAMP, bringing about increased release of thyroxine into the blood stream, and that this is usually not accompanied by adequate synthesis in the gland. Our observation that continuous darkness, which stimulates pineal activity, also brought about an increase in cAMP, concours with our finding of a stimulatory effect of the indolic compounds on thyroid hormone release.

Animals↗

Laboratory tests for acute alcohol consumption: results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence.

BACKGROUND: The WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence aimed partly to evaluate the overall performance and cross-national validity of traditional and new biological markers of alcohol use and abuse. This article focused on the sensitivity and specificity of ethanol and methanol concentrations in plasma, and the 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) ratio in urine, as laboratory tests to identify acute alcohol consumption. Comparison was made with self-reported drinking levels. METHODS: Subjects were recruited in Australia, Brazil, Canada, Finland, and Japan. They were interviewed thoroughly about their alcohol consumption habits, by using the standardized WHO/ISBRA Interview Schedule, and were classified into four categories: nondrinkers, light/moderate drinkers, heavy drinkers (> or =210 g ethanol/week for men, and > or =140 g/week for women), or patients who were receiving treatment for alcohol dependence. Ethanol and methanol determinations in plasma were carried out by headspace gas chromatography. Urinary concentrations of 5HTOL and 5HIAA were determined by using gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively. RESULTS: The baseline levels (in nondrinkers) for methanol and the 5HTOL/5HIAA ratio did not differ markedly between the five populations, except for a considerably higher, but probably artifactual, methanol level in the Finnish plasma samples. Moreover, there were no apparent age or sex differences. The urinary 5HTOL/5HIAA ratio was the most, and ethanol the least, sensitive indicator of recent alcohol consumption, and this was true for the different drinking categories as well as for the five study populations. The highest frequency of elevated test results was observed among those classified as heavy drinkers (e.g., 38% were positive for 5HTOL/5HIAA). However, elevated values also were obtained in nondrinkers and in drinking subjects who denied any intake of alcohol within 2 days before the interview and blood/urine sampling, which suggested a low accuracy of self-reports of alcohol consumption in certain individuals. CONCLUSIONS: The present investigation demonstrated that plasma ethanol and methanol and urinary 5HTOL/5HIAA provide useful exclusion markers for any study of biological parameters that are affected by previous acute ethanol intoxication. The major advantage of methanol and 5HTOL/5HIAA over ethanol is that they can detect recent alcohol consumption even several hours after the ethanol is no longer measurable. The results suggest that the cutoff limits to be used for these markers are not dependent on the country or population to be studied.

Adolescent↗

Utilizing the urinary 5-HTOL/5-HIAA ratio to determine ethanol origin in civil aviation accident victims.

Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of two major serotonin metabolites, 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindole-3-acetic acid (5-HIAA). While the 5-HTOL/5-HIAA ratio is normally very low, previous studies using living subjects have demonstrated that the urinary 5-HTOL/5-HIAA ratio is significantly elevated for 11-19 h after acute ethanol ingestion. Recently, our laboratory developed and validated an analytical method for the simultaneous determination of both 5-HTOL and 5-HIAA in forensic urine samples using a simple liquid/liquid extraction and LC/MS/MS and LC/MS/MS/MS. In this previous work a 15 pmol/nmol serotonin metabolite ratio cutoff was established in postmortem urine, below which it could be conclusively determined that no recent antemortem ethanol consumption had occurred. In the current study this newly validated analytical method was applied to five ethanol-positive aviation fatalities where the origin of the ethanol present could not previously be conclusively determined. In four of the five cases examined the detected ethanol was demonstrated to be present due to postmortem microbial formation, and not consumption, even though some indication of ethanol consumption may have been present.

Accidents, Aviation↗

Galanin immunoreactivity is increased in the nucleus basalis of Meynert in Alzheimer's disease.

A depletion of large cholinergic neurons in the nucleus basalis of Meynert is a consistent finding in Alzheimer's disease (AD). The nucleus basalis of Meynert also contains interneurons and afferents that may modulate its functioning. In the present study we examined neurochemical markers for neuropeptides, amino acid neurotransmitters, and monoaminergic neurotransmitters in postmortem samples of the nucleus basalis in 16 control subjects and 30 patients with AD. There were no significant changes in glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and catecholamines; however, concentrations of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol were significantly reduced. Choline acetyltransferase activity was significantly reduced, consistent with previous reports. Galanin immunoreactivity was significantly increased twofold in the patients with AD, but there were no significant changes in substance P, somatostatin, or neuropeptide Y immunoreactivity. Since galanin inhibits acetylcholine release, and produces cognitive deficits in animals, increased galanin immunoreactivity in the nucleus basalis of Meynert in AD may contribute to the cognitive deficits that characterize the illness.

Aged↗

Determination of urinary indolic metabolites.

A rapid mass spectral assay for tryptophol, 5-hydroxytryptophol, and 3-indoleacetic acid, employing stable-isotope labeled internal standards, is described. The compounds were extracted from urine or buffer with ethyl acetate and quantitatively measured by chemical-ionization mass spectrometry. The calibration curves were linear over a range of 0.06--2.8 microgram/ml. The technique was applied to the analysis of urine from patients with carcinoid tumors. In addition, the first synthesis of 5-methoxy-3-indoleacrylic acid is reported.

Carcinoid Tumor↗

Biological markers in alcoholism.

Alcohol biomarkers include tests indicative of acute or chronic alcohol consumption (state markers), and markers of a genetic predisposition to develop alcohol dependence after chronic exposure (trait markers). While a comprehensive trait marker for alcohol dependence has not been identified, a number of successful state markers for monitoring drinking status are used clinically. These tests provide direct or indirect ways to estimate the amounts of alcohol consumed and the duration of ingestion, and to detect any harmful effects on body functions resulting from long-term misuse. The most obvious method to prove recent drinking is by demonstrating the presence of ethanol in body fluids or breath, but, because ethanol is cleared fairly rapidly from the body, this method is limited to detect only very recent drinking. Measurement of urinary 5-hydroxytryptophol or ethyl glucuronide provide more sensitive methods to disclose recent drinking, because their washout constants are much longer than for ethanol. The liver functions test (GGT, AST and ALT in serum) and the mean corpuscular volume of erythrocytes (MCV) are among the standard diagnostic tools used to identify chronic alcohol exposure. The main disadvantage with these measures is that they have low sensitivity for recent excessive intake, and that raised levels may result from several causes besides heavy drinking, implying a low specificity for alcohol. Carbohydrate-deficient transferrin (CDT), which refers to changes in the carbohydrate composition of serum transferrin, is a more specific marker for identifying excessive alcohol consumption and monitoring abstinence during outpatient treatment. The alcohol biomarkers improves knowledge of drinking patterns in both individuals and populations, and they are also valuable tools for the objective evaluation of treatment efforts. Alcohol markers have, for example, found uses in early identification of at-risk and harmful drinking, and they help to monitor abstinence and relapse in response to outpatient treatment.

Alcoholism↗

Circadian rhythmicity in the stimulation of bioluminescence by biogenic amines and MAO inhibitors in Gonyaulax polyedra.

In the dinoflagellate Gonyaulax polyedra, bioluminescence was investigated in constant darkness. Light emission was stimulated considerably and specifically by the biogenic amines epinephrine, 5-methoxytryptamine, and kynuramine. Various analogues and metabolites of these substances, such as norepinephrine, isoproterenol, phenylephrine, synephrine, metanephrine, dopamine, 3,4-dihydroxymandelic and 3-methoxy-4-hydroxymandelic acids, serotonin, N-acetylserotonin, melatonin, 5-hydroxytryptophol, 5-methoxytryptophol, kynurenine, 4-hydroxyquinoline, 3-hydroxyanthranilic, and quinolinic acids were much less effective. Strong enhancement of bioluminescence, in the range of those obtained with the three stimulatory biogenic amines, was also observed after administration of several compounds acting as MAO inhibitors in mammalian systems, in particular, pargyline, amitriptyline, p-benzoquinone, tranylcypromine, harmaline, and noreleagnine. The responsiveness of cells towards epinephrine, 5-methoxytryptamine, kynuramine, amitriptyline, p-benzoquinone, and noreleagnine varied considerably within the circadian cycle, with the highest stimulations obtained during subjective night. These rhythms can be only partially explained by periodic bioluminescence capacity, and seem to comprise a cyclicity in the sensitivity of cells to the compounds mentioned.

Animals↗