Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamino]-8- azaspiro[4,5]decan-7,9-dione methyl sulphonate), a novel selective 5-HT1A receptor ligand with putative anxiolytic properties, were explored using models of central pre- and postsynaptic 5-HT1A receptor function in the male rat. MDL 73005EF dose dependently decreased the hippocampal 5-HT output measured by in vivo microdialysis in chloral hydrate-anaesthetised rats and this response was antagonised by the 5-HT1A/B receptor antagonist, pindolol. Local administration of MDL 73005EF had no effect on the hippocampal 5-HT output. MDL 73005EF failed to alter basal plasma adrenocorticotropin (ACTH) levels but, in common with pindolol, attenuated the ACTH response to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In contrast to 8-OH-DPAT, MDL 73005EF significantly increased plasma prolactin but apparently not through a 5-HT receptor-mediated mechanism. The results indicate that MDL 73005EF possesses mixed 5-HT1A receptor agonist/antagonist properties, acting as an agonist at presynaptic 5-HT1A receptors controlling 5-HT release and as an antagonist at postsynaptic 5-HT1A receptors mediating ACTH release.
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PMID:Effects of MDL 73005EF on central pre- and postsynaptic 5-HT1A receptor function in the rat in vivo. 196 8

In healthy volunteers, the azapirones--buspirone, ipsapirone, and gepirone--increase plasma cortisol and decrease body temperature; buspirone and gepirone also increase plasma prolactin and growth hormone. Data from animal studies suggest that the ability of azapirones to decrease body temperature and increase corticotropin and corticosterone is mediated by stimulation of presynaptic and postsynaptic serotonin (5-hydroxytryptamine, 5-HT) type 1A subtype receptors, respectively. The mechanism of altered growth hormone and prolactin secretion is less clear. While animal studies implicate changes in dopamine function, current human investigations suggest that 5-HT1A receptors also may be involved in these endocrine responses. Further investigations, using more selective 5-HT receptor antagonists, will be required to resolve this issue.
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PMID:Neuroendocrine effects of azapirones. 197 37

Although (+/-) methylenedioxymethamphetamine (MDMA) has been reported to deplete serotonin (5-HT) and destroy 5-HT terminals in the brains of animals, the functional sequelae of such alterations remain to be established. In the present study, a blunted corticotropin and an enhanced prolactin response to the 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH DPAT) was found in rats treated two weeks previously with a single dose of MDMA (2.0 or 20.0 mg/kg, sc). These results suggest that neurochemical changes produced by MDMA are associated with functional alterations as manifested by abnormal 5-HT receptor-coupled neuroendocrine responses.
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PMID:Diminished corticotropin and enhanced prolactin responses to 8-hydroxy-2(di-n-propylamino)tetralin in methylenedioxymethamphetamine pretreated rats. 198 41

The effects of pindolol on the prolactin (PRL) and growth hormone (GH) responses to intravenous tryptophan (LTP) were studied in eight healthy male volunteers. Pindolol pretreatment (40 mg over 48 h) markedly attenuated the GH response to LTP and modestly, but significantly, reduced the LTP-induced increase in plasma PRL. The disposition of LTP following infusion was not altered by pindolol. While the data are consistent with 5-HT1A receptor mediation of PRL and GH responses to LTP, the intrinsic sympathomimetic actions of pindolol might also be involved in the attenuation of the endocrine responses to LTP.
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PMID:Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan. 200 40

There is extensive pharmacologic evidence that serotonin receptors in the brain can activate the hypothalamic-pituitary-adrenocortical (HPA) axis in rats. Direct-acting serotonin agonists, serotonin uptake inhibitors, serotonin releasers and the serotonin precursor L-5-hydroxytryptophan all increase adrenocorticotrophin (ACTH) and corticosterone release. Serotonin-containing nerve terminals make synaptic contact with corticotrophin-releasing factor (CRF)-containing cells in rat hypothalamus, and serotonin and serotonin agonists stimulate CRF release from isolated rat hypothalamus in vitro. Current evidence, based partly on the ability of selective serotonin receptor antagonists to prevent the increases in ACTH and corticosterone in rats in vivo, implicates 5-HT1A and 5-HT2/5-HT1C receptor subtypes in regulating CRF secretion. The physiologic roles of serotonergic regulation of the HPA axis are not well understood. Serotonin neurons also appear to influence the secretion of other pituitary hormones, especially prolactin and gonadotropins.
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PMID:Serotonin receptors and neuroendocrine responses. 207 82

The effects of serotonergic activation on cold-stimulated thyrotropin (TSH) and prolactin secretion were studied in male rats. Peripheral injections of both 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and 1-(3-chlorophenyl)piperazine (m-CPP), a 5-HT1 agonist, decreased TSH levels. The action of 8-OH-DPAT was antagonized by (+/-)-pindolol, which is known to have 5-HT1 antagonist activity, but not by metergoline or ketanserin. The action of m-CPP was antagonized by ketanserin but not by metergoline. TSH levels were not affected by a 5-HT3 receptor agonist, 2-methyl-5-HT, or by a 5-HT3 antagonist, MDL 72222. Infusion of 8-OH-DPAT into the anterior third ventricle increased TSH levels; 5-HT tended to increase TSH levels, but the effect was not significant. Inversely, infusion of 5-HT, 8-OH-DPAT or m-CPP into the posterior third ventricle decreased TSH levels. The action of 5-HT was counteracted by metergoline, ketanserin and (+/-)-pindolol. Unexpectedly, m-CPP infusion into the anterior third ventricle also inhibited TSH secretion. The prolactin-elevating effects of 5-HT, 8-OH-DPAT and m-CPP were neither consistent nor site-specific. In conclusion, stimulation of both 5-HT1 and 5-HT2 receptors may inhibit TSH secretion, but the exact mechanism underlying the site-dependent action of 5-HT and 8-OH-DPAT on TSH secretion remains to be identified.
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PMID:Complex actions of serotonergic agonists on cold-stimulated TSH secretion in male rats. 214 94

The effects of the selective 5-HT1A receptor agonist gepirone (10 and 20 mg orally) on neuroendocrine function and temperature were assessed using a single-blind cross-over design in 12 healthy male volunteers. Gepirone significantly increased plasma levels of ACTH, beta-endorphin, cortisol, prolactin and growth hormone. Following gepirone there was a significant decrease in body temperature and moderate increases in subjective reports of light-headedness, nausea and drowsiness. Our results are consistent with studies in rodents suggesting that 5-HT1A receptor agonists increase ACTH and prolactin secretion and decrease body temperature. Further investigations are needed to determine if the neuroendocrine and temperature effects of gepirone in humans are mediated by 5-HT1A receptors.
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PMID:The effects of gepirone on neuroendocrine function and temperature in humans. 215 31

Increasing brain 5-hydroxytryptamine (5-HT) function in humans raises plasma concentrations of prolactin, growth hormone and ACTH. Measurement of these hormonal responses provides an index of the functional activity of brain 5-HT pathways. More recent strategies have included the use of directly-acting 5-HT receptor agonists to probe the function of specific receptor subtypes; at present these studies are limited by the questionable selectivity of the agonists employed. Using 5-HT neuroendocrine testing it can be shown that lithium specifically increases the prolactin release mediated by 5-HT pathways. Further studies are needed to determine if this effect is caused by an enhanced sensitivity of post-synaptic 5-HT1A receptors.
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PMID:5-HT neuroendocrine responses during psychotropic drug treatment: an investigation of the effects of lithium. 225 42

1-(m-Trifluoromethylphenyl)-4-(p-aminophenylethyl)piperazine (LY 156163), reported previously to have selective affinity for the 5-HT1A subtype of serotonin receptor in vitro, was studied at doses of 1.25 to 20 mg/kg i.p. in rats to determine if it had properties characteristic of centrally acting serotonin agonists. LY 165163 decreased whole brain concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid, but not of serotonin itself, decreased the rate of accumulation of 5-hydroxyindoleacetic acid after probenecid administration to block its efflux from brain, decreased the rate of decline in serotonin concentration after inhibition of serotonin synthesis with alpha-propyldopacetamide and decreased the accumulation of 5-hydroxytryptophan after decarboxylase inhibition by m-hydroxybenzylhydrazine. LY 165163 also decreased 5-hydroxyindoleacetic acid concentrations in two specific brain regions, striatum and hypothalamus. Serum concentrations of corticosterone and prolactin were increased by doses of LY 165163 that reduced serotonin turnover. These effects are all consistent with evidence from other studies that LY 165163 is a centrally acting serotonin agonist. LY 165163 also increased the concentrations of two dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, measured in whole brain as well as in striatum and hypothalamus, but did not alter dopamine concentration. The accumulation of dopa after decarboxylase inhibition was accelerated by LY 165163. The increases in hormone concentrations in serum and of dopamine metabolite concentrations in brain were not antagonized by pretreatment with metergoline, a serotonin antagonist. The mechanisms of those effects require further study.
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PMID:Central serotonin agonist actions of LY 165163, 1-(m-trifluoromethylphenyl)-4-(p-aminophenylethyl) piperazine, in rats. 243 93

The present study was undertaken to characterize the type of serotonin (5-HT) receptors involved in the control of prolactin (PRL) secretion in male rats. d-Fenfluramine (10 mg/kg i.p.), a potent 5-HT releaser and quipazine, (20 mg/kg i.p.) a 5-HT agonist, caused a marked increase in serum PRL levels. Ritanserin (200 micrograms/kg i.p.), a specific antagonist of 5-HT2 receptors, administered 1 h before the administration of d-fenfluramine or quipazine, completely prevented the PRL-releasing effect of these drugs. Furthermore, the administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) (1.5, 3 and 6 mg/kg i.p.), a compound considered to be a prototypical 5-HT1A agonist, failed to induce any change in serum PRL levels. The same lack of effect on PRL secretion was observed after the administration of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridin-4-yl)-1-H-indole (RU 24969) (1, 3 and 10 mg/kg i.p.), a compound which has been shown to possess a higher selectivity for 5-HT1B receptor subtypes than for 5-HT1A subtypes. These results suggest that 5-HT receptors involved in the control of PRL secretion are of the 5-HT2 type.
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PMID:Pharmacological characterization of serotonin receptors involved in the control of prolactin secretion. 252 99


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