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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aim of the present study was to examine the effect of 5-hydroxytryptamine (5-HT) on K+ current in primary culture of mouse colliculi neurones and to identify the 5-HT receptor subtype that could be involved in this effect. 2. The voltage-activated K+ current of the neurones was partially blocked by 8-bromo adenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP). This effect was mimicked by 5-HT and the action of 5-HT could be antagonized by H7, a non specific protein kinase inhibitor, and by PKI, the specific cyclic AMP-dependent protein kinase blocker. 3. A similar cyclic AMP-dependent blockade of the K+ current was found with renzapride (BRL 24,924) and other 5-HT4 receptor agonists such as cisapride, BIMU 8, zacopride and 5-methoxytryptamine (5-MeOT). ICS 205,930, the classical 5-HT4 receptor blocker, could not be used in this study because it inhibited the studied K+ current by itself. However, the novel 5-HT4 receptor antagonist, DAU 6285 blocked the effects of 5-HT and renzapride on the K+ current. 4. The current was insensitive to the 5-HT1 and 5-HT3 receptor agonists (8-hydroxy-2-(di-n-propylamino) tetralin, RU 24,969, carboxamidotryptamine, 2-CH3-5-HT) as well as to 5-HT1, 5-HT2 and 5-HT3 antagonists (methiothepin, ketanserin, ondansetron [GR 38,032]). Moreover, these antagonists did not affect the actions of the tested 5-HT4 receptor agonists. 5. The present results show that part of the voltage-activated K+ current in mouse colliculi neurones is cyclic AMP-sensitive and the blockade of the current by 5-HT involves the 5-HT4 receptor subtype.The putative implication of 5-HT4 receptors in neuronal plasticity, via a blockade of K+ channels, is discussed.
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PMID:The 5-HT4 receptor subtype inhibits K+ current in colliculi neurones via activation of a cyclic AMP-dependent protein kinase. 132 59

1. The present study investigated the presence of 5-HT3 receptor using 2-methylserotonin (2-Me-5-HT) in the smooth muscle of Mytilus ABRM. 2. 2-Me-5-HT relaxed the acetylcholine-induced contraction in a dose-dependent manner ranging from 10(-6) to 3 x 10(-4) M (pD2 = 5.55 +/- 0.32). 3. 2-Me-5-HT-induced relaxation was antagonized by 3 x 10(-5) M ketanserin in a competitive manner (pA2 = 5.14 +/- 0.1), but not by cypropheptadine, mianserin, MDL 72222 or ICS 205-930 at a concentration of 3 x 10(-5) M. 4. 2-Me-5-HT (3 x 10(-4) M) did not alter the content of cyclic AMP and cyclic GMP in the ABRM. 5. These findings suggested that the 2-Me-5-HT-induced relaxation was mediated through 5-HT2-like receptors and was not linked to cyclic AMP or GMP systems, and, further, that 5-HT3 receptor subtype was not present in the ABRM.
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PMID:Possible site of action of 2-methylserotonin in inducing relaxation of acetylcholine-induced contraction in the molluscan (Mytilus edulis) smooth muscle. 135 10

The novel 5-HT3 receptor antagonist, WAY100289, was examined in two animal models of anxiety: the mouse two-compartment light: dark box, and the rat potentiated acoustic startle paradigm. The activity of WAY100289 in the light: dark box model was also compared with that of the selective 5-HT3 receptor antagonists ondansetron, zacopride, ICS-205,930 and quaternary ICS-205,930 (QICS). WAY100289 mimicked the activity profile of benzodiazepine positive controls in the mouse light: dark box, i.e. WAY100289 markedly and significantly increased the exploratory activity of mice in the more aversive light compartment, at doses of 0.01-1.0 mg/kg s.c. and 0.1-10.0 mg/kg p.o. Zacopride and ondansetron induced comparable effects at doses of 0.001-1.0 mg/kg s.c. ICS-205,930 displayed a markedly biphasic dose-response relationship; being active at 0.01 mg/kg s.c., but not at higher or lower doses. QICS was not active in the light: dark box up to a dose of 10 mg/kg s.c., suggesting that the compound does not enter the brain readily. WAY100289 was also active in the rat potentiated acoustic startle model, significantly attenuating the potentiated startle response at doses of 0.03 and 0.3 mg/kg s.c. The activity profile of WAY100289 in this model resembled that of ondansetron. These data strongly suggest that WAY100289 may possess anxiolytic properties in the clinic.
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PMID:Behavioural studies on WAY100289, a novel 5-HT3 receptor antagonist, in two animal models of anxiety. 135 37

1. Using grease-gap recordings from the isolated superior cervical ganglion of mouse, rat and guinea-pig, we have compared the depolarization evoked by 5-hydroxytryptamine (5-HT) with that evoked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-Me-5-HT). 2. The maximum depolarization induced by 2-Me-5-HT was smaller than that induced by 5-HT in all three species, and particularly in the guinea-pig. 3. The 5-HT2 receptor antagonist ketanserin (1 microM) caused a clear rightward shift of the dose-response curve to 5-HT on the guinea-pig ganglion, but not on the mouse or rat ganglion. Spiperone (0.03 microM) had a quantitatively similar action to ketanserin (0.1 microM) on the 5-HT dose-response curve of the guinea-pig ganglion. Ketanserin had no significant effect on the dose-response curve to 2-Me-5-HT on any of these ganglia. 4. Using 2-Me-5-HT as the agonist, we determined the pA2 values for two 5-HT3 receptor antagonists. The potency of ICS 205-930 varied by approximately 100 fold between the species and that of (+)-tubocurarine varied by over 1000 fold. The differences in the pA2 values of these compounds varied independently among the species. 5. We conclude that 5-HT3 receptors are present on the superior cervical ganglion from the rat, mouse and guinea-pig, but these receptors may be pharmacologically distinct from each other. In addition, the depolarization of the guinea-pig superior cervical ganglion by low concentrations of 5-HT is largely mediated by ketanserin-sensitive receptors.
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PMID:Evidence that the 5-HT3 receptors of the rat, mouse and guinea-pig superior cervical ganglion may be different. 136 27

1. Whole-cell and single-channel voltage-clamp techniques were used to record the 5-HT3 receptor-mediated currents in neurons freshly dissociated from rat superior cervical ganglia. 2. Whole-cell currents elicited by brief pressure ejection of 5-HT (10 microM) reversed at -4.5 mV when extracellular and intracellular solutions mainly contained NaCl and CsCl. The peak current-voltage relation showed modest inward rectification that was fully developed within less than 2 ms of the applied voltage step. 3. With prolonged application of 5-HT (10 microM) using a fast perfusion system, the response desensitized in two phases with fast and slow time constants of 0.57 and 6.0 s at -74 mV. The time constants showed little voltage dependence; however, the relative amplitude of the two components was significantly dependent on voltage. The time course of desensitization was not affected by agents that increase the levels of intracellular cyclic AMP. 4. The relative permeability of the channel was determined from reversal potential changes. The channel passed small cations non-selectively, with permeability ratios (PX/PNa) of 0.93 and 1.24 for Cs+ and K+. The organic cations Tris and glucosamine were measurably permeant with permeability ratios of 0.19 and 0.06. Ca2+ was fairly permeant with a relative permeability of 0.55 in 20 mM solution and of 0.16 when the concentration of CaCl2 was increased to 115 mM. No permeability was detected for Cl-. 5. Fluctuation analysis of the whole-cell current revealed an apparent single-channel current of approximately 0.18 pA at -74 mV. 6. 5-HT-activated single-channel currents were recorded in excised outside-out patches. When 5-HT (10 microM) was delivered by pressure ejection, channel openings appeared rapidly with a delay of 28 ms. The unitary current was about approximately 0.80 pA at -74 mV. The channel activity induced by bath perfusion of 5-HT (0.8 microM) was significantly reduced by 100 nM of the 5-HT3 receptor-specific antagonists 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) or 3-tropanyl-indole-3-carboxylate (ICS 205-930). 7. The single-channel current-voltage relation was non-linear, with moderate inward rectification similar to that of the whole-cell current. The chord conductance of the channel decreased with membrane depolarization from 14.6 pS at -104 mV to only 9.9 pS at -54 mV. Open-time distributions consisted of two components with mean time constants of 0.45 and 2.8 ms at -104 mV. Burst-length distributions were also made up of two components with time constants of 0.45 and 4.6 ms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons. 137 36

The ability of 5-HT3 receptor agonists to modulate the resting efflux or K(+)-evoked release of [3H]5-HT from superfused synaptosomes from the spinal cord of the rat was investigated. Phenylbiguanide did not alter the resting efflux of [3H]5-HIAA or [3H]5-HT or modify the K(+)-evoked release of [3H]5-HT. 2-Methyl-5-HT (10 microM) caused an increase in resting efflux of [3H]5-HIAA, an effect that was blocked by the inhibitor of the uptake of 5-HT fluoxetine. No effect on K(+)-evoked release of tritium was observed. Bufotenine (100-1000 nM) increased the resting efflux of [3H]5-HT and [3H]5-HIAA. These effects were not antagonized by the 5-HT3 antagonist ICS 205-930 but were antagonized by fluoxetine. The drug ICS 205-930 (1 microM) did not alter resting efflux or block the ability of serotonin (30 and 100 nM) to decrease K(+)-evoked release of tritium. Quipazine, a potent antagonist of peripheral 5-HT3 receptors (subnanomolar concentrations), was also unable to alter resting or K(+)-evoked release of [3H]5-HT. It did, however, attenuate the inhibitory effect 5-HT on K(+)-evoked release. The concentrations required were in the micromolar range, consistent with the ability of the drug to antagonize the 5-HT1B autoreceptor. These results support the idea that 5-HT3 receptors do not act as nerve terminal autoreceptors in the spinal cord of the rat.
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PMID:5-HT3 receptors are not involved in the modulation of the K(+)-evoked release of [3H]5-HT from spinal cord synaptosomes of rat. 138 44

Serotonin (5-HT) is involved in the neuroendocrine regulation of prolactin (PRL) secretion as a stimulator. Within the last decade several 5-HT receptor types have been identified, but their individual role in the mediation of the PRL response to 5-HT is only partly understood. We investigated in conscious male rats the effect of different 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytrytophan (5-HTP) which was administered in combination with the 5-HT reuptake inhibitor fluoxetine. 5-HT (0.5-5.0 mg/kg BW i.v.) or 5-HTP (25-100 mg/kg i.p.) in combination with saline or fluoxetine (10 mg/kg i.p.) increased the plasma PRL concentration dose-dependently. Pretreatment with the 5-HT1+2 receptor antagonist methysergide (2.5 mg/kg i.p.) prevented the stimulatory effect of 5-HT or 5-HTP + fluoxetine. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (2.5 mg/kg i.p.) inhibited the PRL response to 5-HT by approximately 80% and to 5-HTP + fluoxetine approximately 100%. A higher dose (10 mg/kg) of the 5-HT2 receptor antagonists possessed only 50% inhibitory effect. Pretreatment with the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the PRL response induced by 5-HT or by 5-HTP + fluoxetine. The maximal inhibitory effect (approximately 80%) was obtained by a dose of 0.1 mg/kg of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of 5-HT1, 5-HT2, and 5-HT3 receptors in the mediation of the prolactin response to serotonin and 5-hydroxytryptophan. 138 14

The effect of antagonists of serotonin (5-HT) receptor subtypes and alpha 2-adrenoceptors was investigated on audiogenic seizures and locomotor activity in DBA/2 mice. 5HT1c receptor antagonists (mianserin and cyproheptadine), 5-HT3 receptor antagonist (zacopride) and 5-HT4 receptor antagonist (ICS 205-930) increased the latency of audiogenic seizures and decreased the severity of convulsions in young (20-27 days old) DBA/2 mice. However, the effect of these antagonists varied in older (30-37 days old) mice. Ketanserin, 5-HT2 receptor antagonist, was devoid of any activity on audiogenic seizures. Yohimbine (0.5 mg/kg, i.p.), an alpha 2-adrenoceptor antagonist, increased the severity of audiogenic seizures, and the anti-convulsant effect of 5-HT receptor subtypes antagonists became more pronounced in the presence of yohimbine. 5-HT3 and 5-HT4 receptor antagonists produced hypolocomotor activity in young mice whereas 5-HT1c and 5-HT2 receptor antagonists were devoid of any effect on locomotor activity. Yohimbine did not induce any effect on locomotor activity but the mice exhibited more pronounced hypolocomotor activity following the administration of 5-HT3, 5-HT4 and 5HT1c receptor antagonists in the presence of yohimbine. However, the results varied with these agents in the older mice. These observations implicate a role of 5-HT1c, 5-HT3, 5-HT4 and alpha 2-adrenoceptors in audiogenic seizures in young DBA/2 mice, and 5-HT3 and 5-HT4 receptors in locomotor activity in these mice. Furthermore, these results also suggest an interaction between 5-HT receptors and alpha 2-adrenoceptors, and differential development patterns of various 5-HT receptor subtypes in the CNS.
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PMID:Effects of 5-HT receptor antagonists on seizure susceptibility and locomotor activity in DBA/2 mice. 139 77

Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model.
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PMID:Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699. 140 95

Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT, 100 microM) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5-HT, 100 microM) depolarized 86% of NTS neurons at resting membrane potential (Vm). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100 microM) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1 microM decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10 microM) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS.
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PMID:5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro. 142 23


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