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)

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 interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (>80%). Partial generalization (defined here as 40% maximal generalization) was seen with the D1 receptor antagonist SCH 23390 (43% maximal generalization), the alpha1-adrenoceptor antagonist prazosin (67%) and the alpha2-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced <25% maximal generalization, including the alpha2-adrenoceptor antagonist yohimbine (24%), the histamine H1 receptor antagonist mepyramine (21%), the D2 antagonist typical neuroleptic haloperidol (23%), the D4 receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2A receptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2C receptor antagonists SB 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3 receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D1 receptor antagonist SCH 23390, or by the 5-HT1A receptor antagonist WAY 100635, when given concomitantly with clozapine. Although the results suggest that muscarinic antagonism plays a major role in the clozapine cue, the results have to be considered in the light of the full generalization to clozapine seen with various antipsychotic agents which have very low affinity for muscarinic receptors, including zotepine, quetiapine, JL13 and PNU 96415 (a finding replicated in rats from the same breeding colony as those which generalized to scopolamine). Thus, generalization to clozapine for antipsychotics with multiple affinities but with low muscarinic affinity is probably mediated by additive or perhaps supra-additive actions at other receptors, although extensive studies with various combinations of drug mixtures are required to validate this hypothesis.
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PMID:Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands. 989 Feb 60

Acute injection of cocaine increases locomotor activity of inbred long-sleep (ILS) mice to a greater extent than inbred short-sleep (ISS) mice. Strain differences in dopamine and/or serotonin (5-HT) neurotransmission could underlie these behavioral differences. Here, we found that dopamine D1, 5-HT(2A) and 5-HT3 receptor antagonists reduced cocaine-stimulated activity selectively in ILS mice. In contrast, 5-HT transporter (SERT) or 5-HT(1A) receptor antagonists potentiated cocaine-stimulated activity in ISS, but not in ILS, mice; this potentiation in ISS mice was abolished by dopamine D1 receptor blockade. Thus, in ILS mice, cocaine-induced activation of D1, 5-HT(2A) or 5-HT3 receptors is sufficient to produce locomotor stimulation. In contrast, ISS mice require pharmacologically increased 5-HT levels, which appear to result in increased dopamine neurotransmission, for cocaine-induced activation. Our results demonstrate strain differences in dopamine/5-HT receptor subtypes and their interactions that contribute to the differential behavioral responsiveness of ILS and ISS mice to cocaine.
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PMID:Differential regulation of cocaine-induced locomotor activity in inbred long-sleep and short-sleep mice by dopamine and serotonin systems. 1547 48