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)

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

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

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

To date, more than two thousand experiments have investigated the behavioral effect of 5-HT-interacting drugs in animal models of anxiety disorders. Most of them have focused on the involvement of drugs interacting with 5-HT1A, 5-HT2A/2C and 5-HT3 receptors. Although numerous results are in line with the classic 5-HT hypothesis of anxiety, suggesting that decreased anxiety is related to decreased activity in central 5-HT neurons and vice versa, paradoxical drug effects have often been found. To explain this variability, several authors point to a determining role of the experimental paradigms used. In fact, an overview of the behavioral data arising from the vast literature indicates that conditioned procedures as well as more ethological-based tests are equal in revealing anxiolytic-like effects of drugs targetting 5-HT1A, 5-HT2A or 5-HT2C receptor subtypes. Furthermore, results obtained in ethologically-based animal models of anxiety with drugs stimulating 5-HT transmission are most consistent with the classic 5-HT hypothesis of anxiety in that they showed an increase in animals' emotional reactivity. Finally, anxiolytic-like effects of 5-HT3 receptor antagonists are in great part revealed by models based on spontaneous behaviors. Taken together, these observations lead to the conclusion that different 5-HT mechanisms, mediated by different receptor subtypes, are involved in the genesis of anxiety.
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PMID:Variability in the effects of 5-HT-related compounds in experimental models of anxiety: evidence for multiple mechanisms of 5-HT in anxiety or never ending story? 911 42

The serotonergic system appears to play a role in behaviors that involve a high cognitive demand and in memory improvement or recovery from impaired cognitive performance, as made evident after administration of serotonin 5-HT2A/5-HT2C or 5-HT4 receptor agonists or 5-HT1A or 5-HT3 receptor antagonists. These serotonin receptor subtypes are localized on 'cognitive' pathways, with the hippocampus and frontal cortex as the main target structures. A better understanding of the role played by these and other serotonin receptor subtypes in cognition is likely to result from the recent availability of new specific ligands and new molecular tools, such as gene knock-out and transgenic mice.
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PMID:Serotonin receptors in cognitive behaviors. 914 56

The role of 5-hydroxytryptamine (5-HT) receptor subtypes in acetylcholine (ACh) release induced by dopamine or neurokinin receptor stimulation was studied in rat striatal slices. The dopamine D1 receptor agonist SKF 38393 potentiated in a tetrodotoxin-sensitive manner the K(+)-evoked [3H]ACh release while SCH 23390, a dopamine D1 receptor antagonist, had no effect. [3H]ACh release was decreased by the dopamine D2 receptor agonist LY 171555 (quinpirole) and slightly potentiated by the dopamine D2 receptor antagonist haloperidol. The selective neurokinin NK1 receptor agonist [Sar9, met(O2)11]SP also potentiated K(+)-evoked release of [3H]ACh. GR 82334, a NK1 receptor antagonist, blocked not only the effect of [Sar9, met(O2)11]SP but also the release of ACh induced by the D1 receptor agonist SKF 38393. Among the 5-HT agents studied, only the 5-HT2A receptor antagonists ketanserin and ritanserin were able to reduce the ACh release induced by dopamine D1 receptor stimulation. Mesulergine, a more selective 5-HT2C antagonist, showed an intrinsic releasing effect but did not affect K(+)-evoked ACh release induced by SKF 38393. Methysergide and methiothepin, mixed 5-HT1/2 antagonists, as well as ondansetron, a 5-HT3 receptor antagonist, showed an intrinsic effect on ACh release, their effects being additive to that of SKF 38393. 5-HT2 receptor agonists were ineffective. However, the 5-HT2 agonist DOI was able to prevent the antagonism by ketanserin of the increased [3H]ACh efflux elicited by SKF 38393, suggesting a permissive role of 5-HT2A receptors. None of the above indicated 5-HT agents was able to reduce the ACh release induced by the selective NK1 agonist. The results suggest that 5-HT2 receptors, probably of the 5-HT2A subtype, modulate the release of ACh observed in slices from the rat striatum after stimulation of dopamine D1 receptors. It seems that this serotonergic control is exerted on the interposed collaterals of substance P-containing neurons which promote ACh efflux through activation of NK1 receptors located on cholinergic interneurons.
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PMID:5-HT2 receptor regulation of acetylcholine release induced by dopaminergic stimulation in rat striatal slices. 920 Apr 94

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.
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PMID:5-HT-induced colonic contractions: enteric locus of action and receptor subtypes. 925 11

The present study compared the effects of a wide range of 5-hydroxytryptamine (5-HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze using spatiotemporal (i.e., open arm time and entries) and ethologically derived measures (i.e., risk assessment activities and directed exploration). The drugs used were 5-HT1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT and flesinoxan) agonists, mixed 5-HT2A/2C receptor antagonists (ritanserin, ketanserin, mianserin, and pirenperone), selective 5-HT3 receptor antagonists (ICS 205-930, MDL 72222, ondansetron, and (RS)-zacopride), and selective (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT reuptake inhibitors. Only buspirone and mianserin produced effects indicative of an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT1A receptor ligands, as well as mianserin, ketanserin, ondansetron, and zacopride, decreased the number of aborted attempts at entry into open arms (risk assessment). In addition, buspirone, mianserin, and zacopride increased head-dipping (directed exploration). Among the 5-HT reuptake inhibitors, zimelidine reduced head-dipping and total entries. The present findings demonstrate that risk assessment responses are sensitive to the action of 5-HT1A receptor ligands, but their modulation by drugs targetting 5-HT2A, 5-HT2C, and 5-HT3 receptors was not convincingly established.
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PMID:Risk assessment behaviour: evaluation of utility in the study of 5-HT-related drugs in the rat elevated plus-maze test. 925 11

We investigated the involvement of serotonin (5-HT) and 5-HT receptors in mediation of stress-induced ACTH secretion in adult male rats, which were pretreated by 5-HT antagonists before restraint-, ether-, cold swim-stress or endotoxin. All stressors potently increased plasma ACTH. Lesion of 5-HT neurons with 5, 7-dihydroxytryptamine injected intracerebroventricularly, into the paraventricular nucleus or into the raphe nuclei, inhibited the restraint stress-induced ACTH response by 50%. Restraint increased the content of 5-HT and its metabolite 5-hydroxyindole acetic acid, in the raphe nuclei, whereas the other stressors had no such effect. Pretreatment with the 5-HT1A receptor antagonist WAY 100635 inhibited the restraint stress- and endotoxin-induced ACTH secretion by 50%. The 5-HT1+2 antagonist methysergide or the 5-HT2 antagonist ketanserin inhibited the restraint- or ether stress-induced ACTH response, and eliminated the endotoxin-induced ACTH response. The 5-HT2 receptor antagonist LY 53857 blocked only the endotoxin-induced ACTH response. Pretreatment with the 5-HT3 receptor antagonist ondansetrone had no effect on stress-stimulated ACTH secretion. The 5-HT3+4 receptor antagonist tropisetrone inhibited the restraint- and ether stress-induced response. The ACTH response to swim stress was not affected by any of the antagonists used. It is concluded that the 5-HT1A, the 5-HT2A and the 5-HT2C receptor, but not the 5-HT3 receptor are involved in the stress-induced ACTH secretion. An involvement of the 5-HT4 receptor is possible. Furthermore, that serotonergic neurons in the raphe nuclei are activated during restraint stress, and that these neurons and neurons in PVN of the hypothalamus, are important for the mediation of the restraint stress-induced ACTH response.
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PMID:Serotonergic involvement in stress-induced ACTH release. 980 68

In slices from immature rat spinal cord, both 5-hydroxytryptamine (5-HT) and the 5-HT2A/C receptor agonists (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT (alpha-Me-5-HT) stimulate phosphoinositide (PI) hydrolysis. PI breakdown is also increased by the 5-HT3 receptor agonist 2-Me-5-HT but not by phenylbiguanide. The effect of either 5-HT or DOI is blocked by selective 5-HT2A receptor antagonists such as spiperone and ketanserin and more markedly by mixed 5-HT2 receptor antagonists, such as ritanserin, methysergide and mesulergine, with higher affinity at the 2C subtype. The effect of 2-Me-5-HT is blocked by 5-HT2 and not by 5-HT3 receptor antagonists, indicating that 5-HT3 receptors do not directly or indirectly take part in PI hydrolysis in the spinal cord. Moreover, lesion with neonatal capsaicin of thin primary afferents to the dorsal spinal cord enhances inositol phosphate formation stimulated by 5-HT or DOI but not by 2-Me-5-HT. This lesion also increases 5-HT2A and 5-HT2C receptor density. After neonatal injection of 5,7-dihydroxytryptamine, which results in a marked loss of 5-HT content in the cord, 5-HT and 5-HT2 receptor agonists also enhance PI breakdown without a concomitant change in receptor number. The results suggest that the 5-HT-stimulated PI response in the rat spinal cord is associated only with the 5-HT2 receptor class, in particular with the 5-HT2C subtype.
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PMID:Pharmacological characteristics and regulation of 5-HT receptor-stimulated phosphoinositide hydrolysis in the rat spinal cord. 1021 91


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