Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direct ion channel.
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PMID:A role for 5HT3 receptors in visual processing in the mammalian retina. 849 2

The effects of duodenal distension on forestomach and abomasal motility were investigated in conscious sheep chronically fitted with intraparietal electrodes, a duodenal cannula, and an intracerebroventricular cannula. Duodenal distensions with a balloon inflated with 40 ml (DD40) of water reduced the frequency of forestomach and abomasal contractions by 45 and 32%, respectively, while distension with 80 ml (DD80) induced a total inhibition. Methysergide, a mixed 5HT1-5HT2 antagonist administered intravenously (200 micrograms/kg) or intracerebroventricularly (20 micrograms/kg) suppressed the DD40-induced inhibition and reduced that induced by DD80. Spiroxatrine, a selective 5HT1A antagonist, intravenously (100 micrograms/kg) or intracerebroventricularly (10 micrograms/kg), suppressed the DD40 and DD80-induced inhibition, which was also attenuated by the 5HT2 antagonist ritanserin given intravenously (200 micrograms/kg) or intracerebroventricularly (20 micrograms/kg). Granisetron, a 5HT3 antagonist, injected intravenously (150 micrograms/kg), abolished the effects of DD40 and DD80 while it had no antagonistic action on DD40 and DD80 when given intracerebroventricularly (15 micrograms/kg). It is concluded that in sheep, duodenal distension inhibits forestomach and abomasal motility through 5HT1A and 5HT2 receptors at the level of the central nervous system and 5HT3 receptors located peripherally.
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PMID:Central and peripheral serotonergic influences on viscerovisceral inhibitory reflex during duodenal distension in sheep. 850 3

A fully automated version of the black and white two-compartment box for mice is presented. The anxiolytic-like effects of the benzodiazepines, diazepam and chlordiazepoxide, were confirmed, and the involvement of serotonergic mechanisms was studied in this animal model of anxiety. The partial 5-HT1A receptor agonists, buspirone and ipsapirone showed anxiolytic-like effects in a limited dose interval. The full agonist hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) was inactive. The non-selective 5-HT1 receptor agonist, eltoprazine, induced marked increases of exploratory behaviour in the white compartment over a broad range of doses. Also pindolol a mixed 5-HT1A/1B and beta-adrenergic receptor antagonist showed anxiolytic-like effects, whereas another compound with a similar profile (-)-, penbutolol and the beta-adrenoceptor antagonist ICI 118,551, was inactive. The 5-HT2A/2C receptor antagonist, ritanserin, showed anxiogenic-like, and the 5-HT3 receptor antagonists, zacopride and ondansetron, showed anixiolytic-like effects. An overall increase of serotonergic activity by means of 5-HT uptake inhibition (citalopram), 5-HT release (fenfluramine) or administration of a 5-HT precursor (1-5-HTP) facilitated exploratory activity in the white compartment. Reduction of serotonergic activity by treatment with the 5-HT depletor p-chloro-phenylalanine methyl ester (PCPA) did not change the exploratory behaviour, but attenuated the response to fenfluramine significantly.
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PMID:Serotonergic mechanisms involved in the exploratory behaviour of mice in a fully automated two-compartment black and white text box. 853 15

The influence of serotonin (5-hydroxytryptamine, 5-HT) on human ureteral smooth muscle was explored in a series of in vitro experiments. 5-HT evoked a dose-dependent contraction of the ureter. The effect of 5-HT was unaltered by blockade of 5HT3 and 5HT4 receptors and muscarinic cholinergic receptors. The 5HT2 receptor antagonist ketanserin (KT; 10(-5)-10(-4) M) and mixed 5HT1/5HT2 receptor antagonist methysergide (MS; 5 x 10(-5) M) inhibited the effect of 5-HT. Since the antagonist dissociation constant at 5HT2 receptors for both KT and MS is found to be approximately 10(-9) M, it is concluded that this contractile effect may have been mediated by some other, as yet uncharacterized 5-HT receptor. We believe that 5-HT is a potential neurotransmitter in the human upper ureteral smooth muscle.
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PMID:Influence of serotonin on the human ureter: an in vitro pharmacological study. 858 66

Serotonin (5-HT) receptors can be classified into at least three, possibly up to seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7. We investigated the role of different serotonin receptor types in a neuroendocrine response to the activation of the serotonergic system. Female immature rats were chosen as an experimental model as it has been shown that during the 3rd week of life, and not at later developmental stages, 5-hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in females and not in males. Besides, at this age, serotonin releases prolactin in both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist) and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist) did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3-chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased both LH and FSH levels, without altering prolactin secretion. The present experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types participate in the release of prolactin at this age. 5-HT1 receptor type may be involved in the release of the three hormones, though a beta-adrenergic component of the response cannot be discarded.
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PMID:Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat. 873 78

It seems that psychopharmacology may be well on its way toward the goal of developing new anxiolytic drug(s) that are fast acting and free from the unwanted effects associated with the traditional benzodiazepines. Several specific candidates exist, based upon rational targeting of neurotransmitter receptors shown to be linked to the neurobiology of anxiety. Thus, partial agonists at the benzodiazepine receptor, such as alpidem, abecarnil, and bretazenil, have highly promising preclinical profiles, and some useful preliminary results in clinical testing of anxiety disorder subjects. Neurosteroids are another interesting set of pharmacologic agents that target the benzodiazepine receptor, have a preclinical anxiolytic profile, and now need to be tested in clinical populations. Targeting of various serotonin (5HT) receptor subtypes is a very active area of current research for novel anxiolytic agents. 5HT3 antagonists may have an anxiolytic profile, but clinical results are still preliminary and need more validation. Of considerable interest is the idea of developing new drugs that act at 5HT1A, 5HT2A, or 5HT2C receptors. It has even been proposed that simultaneous targeting of both 5HT2A and 5HT1A receptors could result in robust anxiolytic agents that will have more immediate onset of action than currently available 5HT1A receptor acting drugs. Neuropeptide receptor agonists and antagonists with anxiolytic properties may represent one of the most striking new classes of potential anxiolytic drugs, but this is an emerging field that still requires considerably more systematic clinical testing. Nevertheless, preclinical studies as well as early clinical studies suggest that at least three neuropeptide receptors are provocative targets for novel anxiolytic agents: namely antagonists for CCK-B receptors, antagonists for CRF receptors, and agonists for neuropeptide Y receptors. Rational development of new pharmacologic agents based upon targeting receptors for those neurotransmitters that regulate the neurobiology of anxiety promises to bring forth a number of exciting therapeutic agents for the treatment of anxiety disorders in the future.
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PMID:Future directions in anxiolytic pharmacotherapy. 874 88

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and receptor subtypes involved in the regulation of jejunal contractions were investigated by close intra-arterial infusions in conscious dogs. Close intra-arterial infusions of 5-HT in short segments of the jejunum stimulated phasic contractions that were blocked completely by atropine, partially by tetrodotoxin, and not affected by hexamethonium. This response was also blocked significantly by 5-HT2A and 5-HT2C receptor antagonists but was not affected by 5-HT1A/5-HT1B, 5-HT3, and 5-HT4 receptor antagonists. Spontaneous phase III contractions were inhibited significantly by 5-HT2A and 5-HT2C receptor antagonists, not affected by 5-HT1A/5-HT1B and 5-HT3 receptor antagonists, and enhanced by 5-HT4 receptor antagonists. Repeated close intra-arterial infusions of 5-HT over several days stimulated giant migrating contractions. We conclude that in the conscious state, 5-HT acts on 5-HT2A and 5-HT2C receptors located on postsynaptic cholinergic neurons in the canine jejunum to stimulate phasic contractions and phase III activity. The 5-HT4 receptors in the canine small intestine may be localized on nonadrenergic, noncholinergic inhibitory neurons; these receptors suppress the amplitude and duration of phase III activity.
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PMID:5-HT-induced jejunal motor activity: enteric locus of action and receptor subtypes. 876 7

1. We have studied the pharmacology of the depolarization by 5-hydroxytryptamine (5-HT) of the guinea-pig isolated superior cervical ganglion (SCG) using the grease-gap technique. We studied the effects of selective and non-selective antagonists on the responses to 5-HT and other 5-HT receptor agonists. 2. We have extended the pharmacology of the 5-HT3 receptor in this preparation by studying the effects of granisetron, BRL 46470 and mianserin on the concentration-response curve (CRC) to 2-methyl-5-HT. As with other 5-HT3 receptor antagonists, these compounds exhibited a lower affinity for guinea-pig 5-HT3 receptors than for rat 5-HT3 receptors. 3. We have confirmed that low concentrations of 5-HT (< or = 1 microM) mediate ketanserin-sensitive responses and higher concentrations of 5-HT also recruit 5-HT3 receptors. The responses to low concentrations of 5-HT were antagonized by low concentrations of ketanserin, spiperone, mianserin, DOI and LSD indicating probably mediation by 5-HT2A receptors. At high concentrations, the hallucinogen, DOI, but not LSD, evoked a ketanserin-sensitive depolarization. 4. Although mianserin could bind to the 5-HT2A receptors in this preparation, we could not demonstrate a down-regulation of depolarizations evoked by these receptors after a 10 day oral treatment with mianserin (10 mg kg-1, daily). 5. 5-Carboxamidotryptamine (5-CT) evoked a prolonged depolarization. Although high concentrations of 5-CT (> or = microM) appeared to activate 5-HT2A receptors, lower concentrations of 5-CT evoked a response with a distinct pharmacology. After studying the action of 20 selective and non-selective 5-HT receptor ligands we believe that this response may be mediated by a novel receptor; but its pharmacology is closest to that of receptors in the 5-HT2 receptor family. Like 5-CT, 5-HT (3-300 microM) could evoke an LSD-sensitive response in the presence of the 5-HT2 receptor antagonist, ketanserin and the 5-HT3 receptor antagonist, tropisetron (all 1 microM). 6. We conclude that 5-HT activates three pharmacologically distinct receptors to depolarize the guinea-pig SCG. Low concentrations of 5-HT appear to activate 5-HT2A receptors. Higher concentrations of 5-HT also activate 5-HT3 receptors and a possible novel 5-HT receptor. The novel receptor could be a species homologue of a 5-HT2 receptor or an, as yet, unclassified 5-HT receptor.
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PMID:Multiple 5-HT receptors in the guinea-pig superior cervical ganglion. 882 38

A human 5-hydroxytryptamine receptor type 3AS (5-HT3R-AS) subunit has been cloned from an amygdala cDNA library. We report the nucleotide and predicted amino acid sequence of the human subunit, which possesses 85% and 84% amino acid sequence identity with mouse and rat 5-HT3R-AS subunits, respectively. Acting on Xenopus laevis oocytes injected with RNA transcripts of the clone, 5-HT and selective 5-HT3 receptor agonists elicited inwardly directed current responses that displayed desensitization. Such currents were blocked in a concentration-dependent manner by selective and nonselective 5-HT3 receptor antagonists but were unaffected by compounds acting at G protein-linked 5-HT receptors. A quantitative comparison of the pharmacological profiles of human and mouse recombinant 5-HT3R-AS receptor complexes revealed differences in the potencies of some antagonist or agonist compounds tested, the most dramatic example being (+)-tubocurarine, which demonstrated an approximately 1800-fold discrepancy in antagonist potency. In view of the small number of sequence substitutions that occur between the human and mouse homologues of the 5-HT3R-AS in the extracellularly located aminoterminal domain, compounds such as (+)-tubocurarine, in conjunction with site-directed mutagenesis, may prove to be valuable in locating amino acid residues that contribute to the ligand binding site(s) of the 5-HT3 receptor. Also, when methodological differences are taken into account, the present study suggests that a homo-oligomeric assembly of human 5-HT3R-AS subunits can account for the distinctive ligand binding properties of human 5-HT3 receptors established in postmortem brain tissue.
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PMID:Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. 884 5

A pharmacologic analysis of the discriminative stimulus of metachlorophenylpiperazine (mCPP) is reported. mCPP and m-trifluoromethylphenylpiperazine generalised, whereas 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole, 6-chloro-2-(1-piperazinyl)-pyrazine, and mesulergine partially generalised to the mCPP discriminative cue. However, although mianserin, methiothepin, ritanserin, mesulergine and N-(1-methyl-5'-indolyl)-N'-(3-pyridyl)urea hydrochloride (SB 200646) all antagonised the effect of 5-hydroxytryptamine (5-HT) on IP3 formation in the rat choroid plexus, they failed to antagonise the mCPP response in the drug discrimination studies. The 5-HT3 receptor antagonist MDL 72222 neither generalised nor antagonised the mCPP cue. These data suggest that neither the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5, 5-HT6, nor 5-HT7 receptors are involved. The response does appear to be mediated by a postsynaptic 5-HT receptor, however, because fenfluramine generalised to the cue. Haloperidol generalises, and amphetamine partially antagonises the mCPP discriminative cue and low doses of apomorphine partially generalises to the mCPP cue, which suggests that a decrease in dopamine neurotransmission may also be involved.
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PMID:Pharmacologic evaluation of the discriminative stimulus of metachlorophenylpiperazine. 884 38


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