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PubMedDate not supplied

Effects of histamine and cimetidine on the levels of serotonin and 5-hydroxyindoleacetic acid in various parts of the digestive tract and in the blood and brain of rats.

In the investigations on male Wistar rats it was demonstrated that histamine (0.05 and 0.5 mg/kg) decreased the serotonin level, without affecting the level of 5-HIAA in the stomach and duodenum. Contrary to this, cimetidine (15, 75 and 150 mg/kg) raised slightly the level of serotonin and decreased the 5-HIAA level in the stomach and duodenum. In the jejunum histamine in the lower dose raised the levels of serotonin and 5-HIAA, and in the higher dose it decreased only the concentration of serotonin. Cimetidine, on the other hand, only in the highest dose increased the serotonin level and decreased significantly the level of 5-HIAA. In the brain a rise of the serotonin level was observed only after histamine. No effects were observed of histamine and cimetidine on the blood serotonin level. Histamine reduced the number of enterochromaffinocytes in the duodenum. These results point to an evident interaction between the histaminergic and the serotoninergic structures in the digestive tract of rats.

Animals↗

PubMed1995

The effect of caerulein-induced acute pancreatitis on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in various rat tissues.

The effects of caerulein-induced acute pancreatitis (AP) on the levels of 5-HT and 5-HIAA in pancreas, liver, brain, kidney and different parts of the digestive tract in rats have been studied. The acute pancreatitis was induced by the continuous intravenous infusion of caerulein in the doses of 5 x 10(-6) g/kg/h and 7.5 x 10(-6) g/kg/h for 12 hours, and the 5-HT and 5-HIAA concentrations were determined by the method of Curzon and Green. The changes evoked by caerulein varied qualitatively and quantitatively between organs. The significant decrease of both 5-HT and 5-HIAA was observed in pancreas, liver, brain and kidney while in the stomach there was a significant fall of 5-HT level accompanied by the relevant increase of 5-HIAA level. In the duodenum, an opposite effect was noticed, the level of 5-HT was higher than normal whereas the 5-HIAA level was reduced. The significant decrease of the 5-HT and 5-HIAA levels in pancreas observed in the present study suggests the importance of 5-HT in the development of acute pancreatitis.

Animals↗

PubMed1978

5-hydroxyindoleacetic acid (5-HIAA) levels in the cerebrospinal fluid of hydrocephalic children before and after ventricular shunting procedure.

21 cases of hypertensive hydrocephalus were investigated for lumbar 5-HIAA before and after operation. Seven groups (posterior fossa tumors) of patients aged between 2 and 12 years were tested after tumor removal; the others (nontumorous hydrocephalus) after ventricular shunting. This last group included 8 patients with noncommunicating hydrocephalus aged between 15 days and 12 years and 6 with communicating hydrocephalus aged between 6 months and 9 years. At the time of the second determination all patients presented an improvement of clinical signs of intracranial hypertension. A correlative analysis of 5-HIAA values before and after operation is made. In tumor cases, preoperative levels were higher than controls, and a significant decrease was found after operation in comparison with preoperative levels. In nontumor cases, a significant decrease was also observed in noncommunicating hydrocephalus, confirming clinical usefulness of the results for controlling the degree of the intracranial hypertension and, in consequence, shunt performance. In communicating cases the results were disappointing, because almost always postoperative levels did not differ from the preoperative ones. Possible interpretations of the data are analyzed.

Cerebrospinal Fluid Shunts↗

PubMed1992

Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement.

We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.

Adult↗

PubMed1980

Chronic morphine administration decreases 5-hydroxytryptamine and 2-hydroxyindoleacetic acid content in the brain of rats.

To study the effects of chronic morphine treatment on cerebral 5-hydroxytryptamine (5HT) metabolism morphine was administered twice daily for 5 or 8 weeks to male Wistar rats. Control rats were treated with 0.9% NaCl solution for the same period. In rats treated chronically with morphine for 8 weeks the cerebral concentrations of 5HT and 5HIAA were reduced by 12--15% (P less than 0.05) at 26--28 h after the last morphine injection (50 mg/kg s.c.). No such decrease was found in the brain of rats treated with morphine for 5 weeks. A test dose of morphine (30 mg/kg s.c. 2h) increased the cerebral concentration and probenecid-induced accumulation of 5HIAA in the rats treated with morphine for 8 weeks almost as much as in the brain of the control rats. Naloxone (10 mg/kg s.c. 2h) did not cause clear changes in the cerebral 5HT or 5HIAA concentration. These experiments suggest that endogenous opioid mechanisms are concerned in the regulation of 5HT neurons and that prolonged morphine treatment weakens these mechanisms. This weakening of endogenous regulation of 5HT neurons, which, however, still respond to acute morphine administration, might be part of the mechanism of compulsive drug use in narcotic addiction. It is possible that these neurons in dependent individuals do not function optimally without exogenous morphine. A similar phenomenon--weakening of endogenous regulation combined with clear responsivity to exogenous opiates--occurs in the cerebral dopamine neurons of rats treated chronically with narcotic analgesics.

Animals↗

PubMedDate not supplied

The determination of 5-hydroxytryptamine, related indolealkylamines and 5-hydroxyindoleacetic acid in the bovine eye by gas chromatography-negative ion chemical ionization mass spectrometry.

Methods were developed for the analysis of 5-hydroxytryptamine, related indolealkylamines (tryptamine, melatonin, 5-methoxytryptamine, N-acetyl-5-hydroxytryptamine and 6-hydroxymelatonin) and 5-hydroxyindole-3-acetic acid (5HIAA) in bovine retina, aqueous and vitreous humours. 5-Hydroxytryptamine and related indolealkylamines were extracted and derivatized to form their corresponding pentafluoropropionyl spirocyclic derivatives. 5HIAA was extracted and derivatized to the corresponding pentafluoropropionamide-trifluoroethyl derivative. Identification and quantitation by gas chromatography-negative ion chemical ionization mass spectrometry was made with reference to deuteriated internal standards. 5-Hydroxytryptamine was present in all (n = 34) retinal samples analysed (20.53 +/- 1.64 ng) while N-acetyl-5-hydroxytryptamine was detected in half of the samples of retina (0.06 +/- 0.02 ng). Melatonin (0.15 +/- 0.06 ng) and tryptamine (0.78 +/- 0.34 ng) were detected in only a small number of retinas. 5-Methoxytryptamine was not present in retina. 5-Hydroxytryptamine was also present in aqueous (0.76 +/- 0.17 ng ml-1 and vitreous (0.35 +/- 0.05 ng ml-1' humours from bovine eye. Tryptamine, melatonin, 5-methoxytryptamine and N-acetyl-5-hydroxytryptamine were not detected in bovine aqueous and vitreous humours. 5HIAA was found in both bovine aqueous (2.03 +/- 0.38 ng ml-1) and vitreous (0.65 +/- 0.06 ng ml-1) humours, but its consistent determination in retina was obviated by interference from spurious peaks.

Animals↗

PubMed1979

[5-Hydroxyindoleacetic acid and creatinine excretion in thermal stress].

The determination of 5-HIIA and creatinine excretion in thermal stress was performed in two series, in the first (I) on 102 healthy men aged 20--45 yrs (58 smokers and 55 non-smokers) and in the second one (II) on 20 men after drinking of 1 1 water immediately before thermal stress. The subjects remained at rest in the climatic chamber for 90 min in the temperature of 45 +/- 1 degrees C and relative humidity of 70 +/- 5 per cent. Thermal stress resulted in a significant increment of body temperature after 45 min and after consecutive 45 min of exposure, and lack of steady state. Creatinine and 5-HIIA were determined in two urine portions after 45 and after consecutive 45 min of exposure. Total amounts of excreted 5-HIIA and creatinine in the first urine portion in (I) and (II) were significantly higher in comparison with normal values; they did not depend on the amount of urine voided. The 5-HIIA excretion was significantly higher in smokers after the first 45 min of exposure only. Total amounts of excreted 5-HIIA and creatinine after another 45 min of exposure in (I) and (II) were significantly lower. The high correlation has been found between excretion of 5-HIIA and creatinine, indicating a similar process of excretion of both substances. Hydratation before the thermal stress exerted advantageous effect on the thermoregulation in men. The results of this study have been discussed in conjunction with the data in literature.

Adult↗

PubMedDate not supplied

Effects of pentagastrin and oxyphenonium on the levels of serotonin and 5-hydroxyindoleacetic acid in different parts of the digestive tract, blood and brain of rats.

In the experiments of Wistar rats it was found that pentagastrin in a dose of 0.6 microgram/kg decreased the level of serotonin and increased that of 5-HIAA in the stomach wall, and in a dose of 3 micrograms/kg it had no effect on these parameters, while in a dose of 6 micrograms/kg it decreased only the serotonin level. Oxyphenonium 0.5 mg/kg increased only the 5-HIAA level in the stomach, and in a dose of 5 mg/kg it decreased also the level of serotonin, In the duodenum these substances remained unchanged after pentagastrin administration, but oxyphenonium 5 mg/kg caused a significant fall of serotonin and increase of 5-HIAA, which was associated with a decrease in the number of enterochromaffin cells. In the small intestine pentagastrin 0.6 micrograms/kg increased the serotonin level and decreased that of 5-HIAA, in a dose of 3 micrograms/kg it decreased only the 5-HIAA level, and in the 6 micrograms/kg dose it had no effect on the levels of these substances. Oxyphenonium increased only the intestinal 5-HIAA level but only when administered in a dose of 5 mg/kg. In the brain both higher doses of pentagastrin decreased the serotonin level, and all three doses raised significantly the 5-HIAA level. Oxyphenonium in the higher dose raised the brain serotonin level, but was without effect on the 5-HIAA level. The blood serotonin level was not changed by pentagastrin and oxyphenonium.

Animals↗

PubMed1989

[Study on the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar cerebrospinal fluid (CSF) in neurological diseases].

Experimental evidence has shown that the amount of 5-HIAA in the CSF reflects the metabolism of serotonin in the brain if this metabolite is eliminated from the brain and flows into the CSF at a constant rate. We studied the concentration of 5-HIAA in the lumbar CSF in several neurological diseases to elucidate the alteration in abnormalities of serotonin metabolism. The concentration of 5-HIAA in the CSF was measured in 94 patients with cerebral infarction, 30 with vascular dementia, 25 with dementia of the Alzheimer type, 28 with Parkinson's disease and 6 with hypoxic encephalopathy. Patients with cerebral infarction were classified into 24 with a solitary cerebral infarct and 70 with multiple cerebral infarcts. Patients with Parkinson's disease were subdivided into 12 with various psychiatric symptoms including depressive state, hallucination and/or intellectual impairment and 16 without psychiatric symptoms. Patients with hypoxic encephalopathy consisted of 5 with apallic syndrome and one patient with Lance-Adams syndrome. The concentration of 5-HIAA in solitary cerebral infarct, multiple cerebral infarcts and vascular dementia did not exhibit a significant difference from that in control cases (54.6 +/- 23.1 ng/ml). But patients with dementia of the Alzheimer type (34.5 +/- 10.9, p less than 0.001) showed a significantly lower concentration. This fact seems to reflect the pathological finding that the number of large neurons is decreased and neurofibrillary tangles are increased in the nucleus raphe dorsalis of patients with Alzheimer type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Evaluation of intraplatelet and urinary 5-hydroxytryptamine (5-HT), and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels in patients with toxemia of pregnancy.

Toxemia of pregnancy is considered to represent a disorder of activated blood coagulation. To identify possible indicators for evaluating the clinical course of toxemia, we measured the intraplatelet and urinary levels of 5-HT and its urinary metabolite, 5-HIAA in 25 patients with toxemia vs. 29 non-toxemic pregnant women. 5-HT and 5-HIAA were assayed by high performance liquid chromatography (HPLC). During the 24-34 weeks of gestation, the toxemic patients and the non-toxemic women each had low intraplatelet levels of 5-HT which didn't differ significantly. A significant (p < 0.05) decrease in intraplatelet 5-HT was observed in the toxemic patients vs. the non-toxemic women after the 35th week of gestation until delivery. The untake of exogenous 5-HT by platelets was increased in the toxemic patients, and their urinary (5-HT+5-HIAA) value increased significantly (p < 0.05) as compared with the non-toxemic women after the 35th week of gestation until delivery. A decrease in the intraplatelet level of 5-HT and an increase in the urinary level of (5-HT+5-HIAA) were observed in the toxemic patients, findings that paralleled the progression of this disorder. Serial measurements of intraplatelet and urinary levels of 5-HT and urinary levels of 5-HIAA in the toxemic patients revealed a significant correlation between disease activity and those levels. These observations support the concept that the measurement of intraplatelet and urinary levels of 5-HT and of urinary levels of 5-HIAA may be useful in following the clinical course of the toxemic patients.

Adult↗

PubMed1995

Distinguishing ingested ethanol from microbial formation by analysis of urinary 5-hydroxytryptophol and 5-hydroxyindoleacetic acid.

During the metabolism of ethanol, the metabolic conversion of serotonin (5-hydroxytryptamine) is altered, and, as a consequence, the ratio of 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) excreted in urine increases appreciably. The ratio of metabolites remains elevated for several hours after ethanol is no longer detectable. In the present study, urine specimens were supplemented with glucose and Candida albicans, a common human pathogenic yeast, and the formation of ethanol and the changes in the 5HTOL/5HIAA ratio were examined during one week of storage. Despite the production of high concentrations of ethanol (peak level 171 mmol/L, or 788 mg/dL), the 5HTOL/5HIAA ratio remained constant. The urinary 5HTOL/5HIAA ratio was also compared with urinary and blood ethanol levels in specimens selected at random during forensic autopsies. Elevated 5HTOL/5HIAA ratios were found in all specimens with detectable urinary ethanol. Some specimens showed elevated ratios of serotonin metabolites even though no ethanol was detected, indicating that these subjects had consumed ethanol prior to death but that the concentration had already returned to zero or was below the detection limit. In one case, postmortem ethanol formation was suspected, because blood ethanol concentration was 16.8 mmol/L (77 mg/dL) whereas urinary ethanol was zero. The urinary 5HTOL/5HIAA ratio fell within normal limits, which confirmed the suspicion of postmortem ethanol synthesis in the blood specimen. The present results indicate that the 5HTOL/5HIAA ratio in urine provides a useful method to distinguish between ethanol that might have been synthesized postmortem, or generated in vitro, from ethanol excreted in urine as a result of drinking.

Adult↗

PubMed1971

Regional and subcellular changes in the concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat brain caused by hydrocortisone, DL- -methyl-tryptophan l-kynurenine and immobilization.

1. In agreement with previous findings on whole brain, the intraperitoneal injection of hydrocortisone, DL-alpha-methyltryptophan or L-kynurenine decreased the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) in different regions of the rat brain.2. Hydrocortisone caused similar decreases in the concentrations of both 5-HT and 5-HIAA, suggesting decreased 5-HT synthesis.3. Changes in the concentration of 5-HIAA after hydrocortisone corresponded significantly to those after alpha-methyltryptophan. Changes in the concentration of 5-HT did not correspond, possibly due to falsely high 5-HT values because of interfering material derived from alpha-methyltryptophan.4. In general, kynurenine caused larger decreases in the concentration of 5-HT than in the concentration of 5-HIAA.5. In agreement with previous findings with whole brain, immobilization of rats for 5 h decreased the concentration of 5-HT and increased that of 5-HIAA in most brain regions.6. The order of the percentage decreases in the concentrations of 5-HIAA 6 h after hydrocortisone injection was, in decreasing order: hypothalamus, striatum, cerebellum, mid-brain, pons + medulla and cortex. The percentage increases after immobilization for 5 h were in the reverse order.7. The differences between the percentage decreases in the concentration of 5-HIAA after hydrocortisone and the percentage increases after immobilization were very similar in all regions except the hypothalamus. This is consistent with immobilization stress increasing the firing rate of 5-hydroxytryptaminergic neurones similarly in different regions.8. During the first 3 h of immobilization the concentrations of 5-HIAA in the hypothalamus and in the rest of the brain increased approximately in parallel. Between 3 and 5 h, 5-HIAA returned to control concentrations in the hypothalamus while continuing to rise in the rest of the brain.9. Relative changes in the concentration of 5-HT in particulate and supernatant fractions after the various treatments were comparable except 2 h after kynurenine injection when the concentration 5-HT fell in the particulate but not in the supernatant fraction. The concentration of 5-HT did fall in the latter, though more slowly than in the former fraction, suggesting a concentration of amine synthesizing organelles in particulate material.

Animals↗

PubMed1979