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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 purpose of the present study was to investigate the effect of microinjection of serotonin (5-HT) and selected 5-HT receptor subtype agonists and antagonists into the caudal nucleus raphe obscurus on gastrointestinal motor activity in urethane-chloralose anesthetized rats. Serotonin (0.6-18.0 nmol) dose-dependently increased intragastric pressure, and this effect was abolished by peripherally administered atropine (0.5-1.0 mg/kg, i.v.). Microinjection of a 5-HT1A receptor agonist, 8-hydroxy-N,N-dipropyl-2-amino-tetralin hydrobromide (0.06-12.0 nmol), a 5-HT1C/2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (4.5 and 18.0 nmol), as well as a 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (0.6-18.0 nmol), also resulted in increases in intragastric pressure. The gastric excitatory effect of 5-HT (6.0 nmol) was markedly reduced by prior microinjection of a 5-HT1/2 receptor antagonist, methiothepin (200 nmol), into the same site, as well as by i.v. administration of a 5-HT2/1C antagonist, ketanserin (2.5 mg/kg). The effect of 5-HT (6.0 nmol) on intragastric pressure was completely blocked by i.v. administration of a mixture of the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazinehydrobromide++ + (3.5 mg/kg), ketanserin (2.5 mg/kg) and the 5-HT3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (2.5 mg/kg). These results indicate that 5-HT activates gastric motor function in the caudal nucleus raphe obscurus via a vagally mediated pathway and that the activation of multiple 5-HT receptor subtypes is required for the gastric excitatory effect of 5-HT.
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PMID:Serotonin microinjected into the nucleus raphe obscurus increases intragastric pressure in the rat via a vagally mediated pathway. 809 47

Biochemical and electrophysiological approaches were used to assess the possible changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat brain after a long-term treatment with cericlamine [2-(3,4-dichlorobenzyl)-2-dimethylamino-1-propanol], a novel serotonin reuptake inhibitor with antidepressant properties. Possible changes in other serotonin receptor binding sites (5-HT2A, 5-HT2C and 5-HT3) were also investigated after this treatment. Cericlamine was injected for 2 weeks at a dose (16 mg/kg i.p., twice daily) that ensured complete prevention of 4-methyl-alpha-ethyl-meta-tyramine-induced depletion of brain serotonin. In vitro binding and quantitative autoradiographic studies showed that neither 5-HT1A, 5-HT2A, 5-HT2C nor 5-HT3 receptor binding sites in various brain areas were affected by the 14-day treatment with cericlamine. Although forskolin-stimulated adenylate cyclase activity was significantly increased in hippocampal homogenates from cericlamine-treated rats, the reduction in this enzymatic activity due to 5-HT1A receptor stimulation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unchanged in these animals as compared with controls. In contrast, in vitro and in vivo electrophysiological recordings of serotoninergic neurons in the dorsal raphe nucleus revealed a clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus the potency of 8-OH-DPAT and ipsapirone to depress the firing rate of these neurons in brain stem slices was significantly reduced after the 2-week treatment with cericlamine. In vivo, the potency of an injection of cericlamine to inhibit the discharge of serotoninergic neurons was also markedly less in rats that had been pretreated for 2 weeks with this drug as compared with controls. However, the inhibitory effects of systemically injected 8-OH-DPAT and ipsapirone on the electrical activity of serotoninergic neurons were as pronounced in cericlamine-treated rats as in controls. In addition, the reduction in serotonin synthesis due to an acute treatment with 8-OH-DPAT (0.1 or 0.3 mg/kg s.c.) was not significantly different in both groups of rats. These data support the idea that postsynaptic (in the hippocampus) and somatodendritic (in the dorsal raphe nucleus) 5-HT1A receptors are differently regulated in the rat brain, because only the latter receptors desensitized after a long-term blockade of serotonin reuptake by cericlamine. They also suggest that the inhibitory influence of systemically administered direct 5-HT1A agonists such as 8-OH-DPAT and ipsapirone on the electrical and metabolic activity of serotoninergic neurons does not result solely from the stimulation of somatodendritic 5-HT1A autoreceptors.
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PMID:Central pre- and postsynaptic 5-HT1A receptors in rats treated chronically with a novel antidepressant, cericlamine. 813 56

The actions of 5-hydroxtryptamine (5-HT)1A and 5-HT4 receptor agonists on fast excitatory postsynaptic potentials (EPSPs) in myenteric neurons of guinea pig ileum were studied in vitro. Intracellular electrophysiological methods were used to record EPSPs. 5-HT (0.1 microM), 5-carboxamidotryptamine (0.001-0.1 microM), 8-hydroxydipropylaminotetralin (0.003-0.3 microM), and 5-methoxytryptamine (5-MeOT; 0.3 microM) inhibited EPSPs. Agonist inhibition of EPSPs was blocked by the 5-HT1A receptor antagonists, spiperone and NAN-190. In the presence of NAN-190 (0.3 microM), 5-HT (0.001-0.1 microM) increased EPSP amplitude. 5-MeOT (0.001-0.1 microM), renzapride (0.01-0.3 microM), cisapride (0.01-1 microM), and BIMU 8 (0.003-0.1 microM) increased EPSP amplitude but did not change the membrane potential of any neuron. EPSP potentiation induced by each agonist was blocked by the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM), but not by the 5-HT3 receptor antagonist, ondansetron (1 microM). Potentiation of fast EPSPs by 5-HT (0.1 microM) desensitized, whereas renzapride (0.1 microM) responses did not. Desensitization induced by BIMU 8 was variable. These data indicate that enteric 5-HT1A and 5-HT4 receptors function to inhibit and facilitate transmitter release, respectively. 5-HT4-mediated facilitation of ganglionic neurotransmission could contribute to the prokinetic effects of cisapride and renzapride.
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PMID:5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. 814 Dec 96

In previous studies, we showed that light-induced Fos protein expression in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to characterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induced Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered during the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspirone, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1.3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8-OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists. 819 64

Dumuis and colleagues (1988) in their investigation of a 5-HT receptor positively linked to adenylate cyclase in the central nervous system, concluded that the receptor was not 5-HT1, 5-HT2 or 5-HT3-like and suggested that it belonged to a new class of 5-HT receptor called 5-HT4. A similar, if not identical receptor was located by Craig and Clark (1990) in the guinea pig ileum and a functional role for the peripheral 5-HT4 receptor has since been established in many species to mediate muscle contraction or relaxation within the gut and positive inotropic effects in the heart. In contrast, a functional role for central 5-HT4 receptors has remained obscure. Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH-DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation. 5-Hydroxytryptophan has the opposite effect exacerbating the behavioural response to the aversive situation. But an anxiolytic profile is revealed by co-treatment with ritanserin plus 5-hydroxytryptophan. The drug-induced anxiolytic profiles are inhibited by SDZ205-557 and a high dose of tropisetron. Both compounds are 5-HT3/5-HT4 receptor antagonists yet the selective 5-HT3 receptor antagonist ondansetron fails to inhibit the drug-induced anxiolytic profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacology of the 5-HT4 receptor. 820 Dec 42

1. The pharmacological properties of RS 23597-190 (3-(piperdine-1-yl)-propyl-4-amino-5-chloro-2-methoxy benzoate hydrochloride) have been studied in vitro and in vivo. 2. RS 23597-190 competitively antagonized 5-HT4 receptor-mediated relaxations of rat, carbachol precontracted oesophageal muscularis mucosae, (pA2 = 7.8 +/- 0.1; Schild slope = 1.2 +/- 0.2). Affinity estimates (-log KB) at 5-HT4 receptors using either renzapride or SC-53116 as agonists yielded a -log KB value of 8.0 +/- 0.01. In contrast, RS 23597-190 failed to antagonize contractile responses to 5-HT of guinea-pig ileal 5-HT3 receptors, even at concentrations up to 10 microM. 3. Increases in short-circuit current, induced by 5-HT, were studied in guinea-pig ileal mucosal sheets. Concentration-response curves to 5-HT were biphasic, with the high potency phase to 5-HT inhibited by RS 23597-190 and mimicked by 5-methoxytryptamine. The -log KB value for RS 23597-190 at the high potency phase was 7.3 confirming that 5-HT4 receptors mediated the high potency phase. 4. In rat isolated vagus nerve, 5-HT elicited a slow, maintained depolarization at low concentrations and a rapid, transient depolarization at higher concentrations. The high potency, slow depolarizing phase to 5-HT was abolished selectively in the presence of 1 microM RS 23597-190 and the low potency phase was abolished selectively in the presence of 1 microM ondansetron. These data confirm that 5-HT4 and 5-HT3 receptors mediated slow and fast depolarization responses, respectively. 5. At 5-HT3 binding sites in membranes from NG 108-15 cells, labelled by [3H]-quipazine, RS 23597-190 exhibited an apparent affinity (- log Ki) of 5.7 +/- 0.1. At 5-HT3 receptors in membranes from rat cerebral cortex, labelled by [3H]-RS 42358-197, the apparent affinity (- log Ki) of RS 23597-190 was also 5.7 +/- 0.1. In both studies, Hill coefficients were not significantly different from unity. At 5-HT1A, 5-HT2,muscarinic M1, M2, M3, M4 and dopamine D1 and D2 receptors, RS 23597-190 exhibited low apparent affinities, with all - log Ki values less than 5.5.6. Intravenous infusion of RS 23597-190 in the conscious, restrained rat antagonized the von Bezold Jarisch reflex induced by 2-methyl 5-HT, with an ID50 of 300 microg kg-1 min-1, i.v. In the anaesthetized,bilaterally vagotomized micropig, RS 23597-190 (6 mg kg-1, i.v.) antagonized 5-HT-induced tachycardia with a half-life of 77 (63-99) min. Transient arrhythmic effects were noted after administration of the compound.7. In conclusion, RS 23597-190 acts as a high affinity, selective competitive antagonist at 5-HT4 receptors. Thus, the compound appears to be a useful tool for 5-HT4 receptor identification in vitro. In vivo, the compound is rapidly metabolized in pigs such that 5-HT4 blockade is not maintained. However,in the rat, when given by infusion, RS 23597-190 antagonizes 5-HT3 mediated responses, at doses consistent with a low affinity 5-HT3 receptor. These data suggest that, under appropriate experimental conditions, RS 23597-190 may also be used in vivo to characterize further 5-HT4 receptor function.
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PMID:RS 23597-190: a potent and selective 5-HT4 receptor antagonist. 822 Aug 71

The binding of [3H]endo-N-(8-methyl-8-azabicyclo[3.2.1.]oct-3-yl)- 2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazole-1-carboxamide hydrochloride ([3H]BIMU-1) a benzimidazolone with high affinity for 5-hydroxytryptamine (5-HT)3 and 4 5-HT3 and 5-HT4 receptors, was characterized in NG-108 cells and guinea pig hippocampus. Specific, heat-sensitive, binding of [3H]BIMU-1 was detected in both NG-108 cells and guinea pig hippocampus. In NG-108 cell membranes, a portion of the specific binding was displaced by 5-HT3 receptor ligands with affinities and specificity consistent with the labeling of 5-HT3 receptors. The residual specific binding was insensitive to serotonin (Ki > 1 mM) but was displaced by haloperidol (Ki of 50 nM). In guinea pig hippocampal membranes [3H]BIMU-1 binding was insensitive to serotonin but was displaced by haloperidol, and 1,3-di-o-tolyl-guanidine with affinities appropriate for the labeling of a sigma binding site (Ki of 6.3 and 31 nM, respectively). The affinity profile of ligands displacing [3H] BIMU-1 binding in guinea pig hippocampus was consistent with the selective labeling of a sigma-2 binding site because the sigma-1 selective benzomorphans, (+)-pentazocine and (+)-N-allylnormetazocine, only weakly displaced the binding (Ki greater than 1 microM). The affinity of BIMU-1 for sigma-2 binding sites (Ki = 32 nM) was 200-fold greater than that for sigma-1 binding sites (Ki = 6.3 microM), dopamine (D1 and D2), other serotonin (5-HT1A, 5-HT2A, 5-HT2C) and muscarinic (M1, M2, M3 and M4) receptors (Ki > 10 microM). The distribution of haloperidol-sensitive [3H]BIMU-1 binding was also consistent with the labeling of sigma-2 binding sites. These data suggest that [3H]BIMU-1 selectively labels sigma-2 binding sites in guinea pig hippocampus. [3H]BIMU-1, under appropriate experimental conditions, is thus the first sigma-2 binding site radioligand to be characterized.
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PMID:[3H]BIMU-1, a 5-hydroxytryptamine3 receptor ligand in NG-108 cells, selectively labels sigma-2 binding sites in guinea pig hippocampus. 824 71

5-Hydroxytryptamine (5-HT) is a mitogen for selected cell types. We have reported that 5-HT is an autocrine growth factor for functioning human pancreatic carcinoid (BON) cells; autocrine growth effect is transmitted by 5-HT1A but not 5-HT1C/2 receptors, activation of which decreases cyclic AMP production through a pertussis toxin-sensitive inhibitory GTP-binding protein. In this study, the effect of 5-HT3 receptor antagonist, ondansetron, on BON was examined. Ondansetron did not affect growth of BON cells and also affected neither stimulation of phosphatidylinositol hydrolysis or inhibition of cyclic AMP production evoked by 5-HT in BON cells. Ondansetron, however, inhibited mobilization of intracellular calcium evoked by 5-HT. Present findings suggest that BON cells possess 5-HT3 receptors, but their roles in pancreatic carcinoid cells are still unknown.
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PMID:Effect of 5-HT3 receptor antagonist (ondansetron) on functioning human pancreatic carcinoid cells. 825 12

The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine and the 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were examined in a dietary paradigm that appears to be sensitive to 5-HT-induced carbohydrate suppression. In this paradigm, deprived rats are provided with a nutritionally complete hydrated chow mash diet together with an optional carbohydrate supplement of powdered Polycose. Both d-fenfluramine and DOI produced a clear suppression of total energy intake and carbohydrate (Polycose) intake. However, the mechanisms underlying these effects are different. The effect of d-fenfluramine in this paradigm was attenuated by the 5-HT1/5-HT2 receptor antagonist metergoline and partially attenuated by the 5-HT1A/5-HT1B receptor antagonist (+/-)cyanopindolol. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS-205,930), the 5-HT2/5-HT1C receptor antagonist ritanserin, or the peripheral 5-HT receptor antagonist xylamidine. However, the effect of DOI in this paradigm was significantly attenuated by ketanserin but was not antagonised by either ritanserin or (+/-)cyanopindolol. Therefore, the suppressive effect of these two 5-HT drugs on total and Polycose intake appears to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5-HT2 receptors (DOI).
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PMID:5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d-fenfluramine and DOI. 826 89

C57BL/6 mice exhibit acute transient decreases in lung conductance (GL) and dynamic compliance (Cdyn) after intravenous administration of serotonin (5-HT). To identify the specific agonist receptor subtypes responsible for this bronchoconstriction, we measured changes in pulmonary function in C57BL/6 mice in response to intravenous infusion of 5-HT receptor subtype-selective agonists and to 5-HT in the presence of antagonists selective for the 5-HT2 or 5-HT3 receptor subtypes. Agonists selective for the 5-HT1A/1B/1D or 5-HT3 receptor subtypes induced minimal or undetectable pulmonary responses, whereas infusion of alpha-methyl-5-hydroxytryptamine, a 5-HT2 receptor-selective agonist, led to dose-related decreases in Cdyn and GL. The selective 5-HT3 receptor antagonist, LY278584 maleate, (1.0 mg/kg i.v.) caused no detectable reduction in the response to 100 micrograms/kg of 5-HT. In contrast, treatment with the 5-HT2 receptor antagonist LY53857 (10 micrograms/kg i.v.) resulted in a significant diminution of the pulmonary response observed after infusion of 100 micrograms/kg of 5-HT. Dose-response relationships were established for 5-HT in experiments in which each mouse was treated with a single dose of 5-HT without antagonist or after LY53857. Compared with responses to doses of 5-HT of more than 100 micrograms/kg in the absence of antagonist, pulmonary responses to 5-HT after infusion of 10 micrograms/kg of LY53857 were significantly reduced; 100 micrograms/kg of LY53857 nearly abolished the responses to all doses of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-induced pulmonary responses are mediated by the 5-HT2 receptor in the mouse. 830 45


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