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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. 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

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

Grease-gap recordings revealed that 5-hydroxytryptamine (5-HT) depolarized the ferret vagus nerve (pEC50 = 4.9). This response was mimicked by 2-methyl-5-HT and 1-phenylbiguanide, but not by 5-carboxamidotryptamine. Paroxetine (1 microM) or ketamine (10 microM) did not potentiate the response. Ketanserin (1 microM) did not reduce the depolarization, but four 5-HT3 receptor antagonists did. It is concluded that 5-HT depolarizes the ferret vagus nerve via 5-HT3 receptors, but these receptors may differ pharmacologically from those in other species.
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PMID:Pharmacology of the 5-hydroxytryptamine-induced depolarization of the ferret vagus nerve in vitro. 145 88

This study describes a component of 5-HT-evoked depolarization of the rat isolated vagus nerve which was unaffected by the 5-HT3 receptor antagonist ondansetron. A grease-gap extracellular recording technique was used. Ondansetron (10-100 nmol/l) displaced the 5-HT concentration-response curve to the right yielding a pA2 value of 8.6 (8.5-8.8), consistent with 5-HT3 receptor antagonism, and revealing a component of the 5-HT response which was resistant to ondansetron blockade. In the presence of ondansetron (100 nmol/l) the maximum depolarization in the resistant phase was 15.5 (12.6-19.2)% of the initial maximum response to 5-HT and the pEC50 value was 7.0 (6.7-7.3). The mechanism of the ondansetron-resistant component of the 5-HT response resembled a 5-HT4-receptor-effect in being absent in preparations equilibrated with 5-methoxytryptamine (10 mumol/l) and antagonised by ICS 205930 (tropisetron, pA2 6.4). 5-Methoxytryptamine alone was an agonist in the vagus nerve with a maximum response similar to that of the ondansetron resistant phase of the 5-HT response. Similarly renzapride alone evoked small depolarizations of this preparation but antagonized the ondansetron resistant phase of the 5-HT response (pA2 7.3-7.4). These effects of 5-methoxytryptamine and renzapride are also consistent with a 5-HT4 receptor mechanism. Ketanserin (1 mumol/l) and methysergide (1 mumol/l) had little effect on responses to 5-HT. The depolarization evoked by this putative 5-HT4 receptor mechanism was small but prolonged and appears to mask and after-hyperpolarizing phase of the 5-HT response in this tissue.
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PMID:A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor. 147 Feb 21

To improve the pharmacological characterization of the receptors mediating 5-hydroxytryptamine (5-HT)-induced apnea the inhibitory effects of exogenous 5-HT on respiration and phrenic nerve activity (PNA) were studied in anesthetized rats. The effects of putative 5-HT receptor agonists and antagonists on respiratory parameters were examined. During spontaneous respiration the bolus i.v. injection of 5-HT (3.125-25 micrograms/kg) produced a transient apnea, the duration of which increased in a dose-related manner. In addition, during artificial respiration 5-HT produced a silent response of PNA, the duration of which increased dose-dependently. These responses were significantly antagonized by GR38032F, a selective 5-HT3 receptor antagonist. Ketanserin (100 micrograms/kg) and methysergide (100 micrograms/kg), 5-HT2 receptor antagonists, also inhibited the 5-HT-induced apnea. These effects of 5-HT on respiration were mimicked by 2-methyl-5-HT (3.125-25 micrograms/kg), a selective 5-HT3 receptor agonist, and by a high dose of alpha-methyl-5-HT, a 5-HT2 receptor agonist, but not by 5-carboxamidotryptamine, a 5-HT1-like receptor agonist. Lung compliance was greatly reduced and lung resistance greatly increased by 5-HT (3.125-25 micrograms/kg). The 5-HT-induced changes in lung compliance and lung resistance were antagonized markedly by both ketanserin (100 micrograms/kg) and methysergide (100 micrograms/kg), but not by GR38032F (100 micrograms/kg). Bilateral vagotomy above the nodose ganglia completely prevented both the changes in PNA and the apnea induced by 5-HT. These actions of 5-HT were not prevented, however, by cervical vagotomy below the level of the nodose ganglion. On the other hand, this cervical vagotomy completely blocked the alpha-methyl-5-HT-induced apnea.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of 5-hydroxytryptamine-induced apnea in the rat. 153 63

1. The effects of intra arterial (i.a.) injections of 5-hydroxytryptamine (5-HT, 1-100 micrograms) on the discharge of (a) identified articular high threshold mechanoreceptors and (b) unidentified chemosensitive receptors in the ankle joint have been studied electrophysiologically in anaesthetized normal and arthritic rats. Recordings were made from a fine branch of the medial plantar nerve. 2. 5-HT increased the mechanical responsiveness of high threshold nociceptive mechanoreceptors with C and A delta fibre afferents in both normal and adjuvant-arthritic rats. Receptors in arthritic joints were more sensitive to 5-HT than were those from normal joints. 3. 5-HT produced a complex response from both types of articular receptors following i.a. injection. Two separate components were identified: (a) a fast transient burst of activity was obtained within 10 s of this injection in 66% of units from normal animals and 45% from arthritics, followed by (b) a delayed slow longer-lasting excitation seen in 62% of the units examined from normals and 77% of units from arthritic rats. 4. Increased mechanoreceptor responsiveness produced by 5-HT was reduced or abolished by the 5-HT3 receptor antagonists studied (MDL 72222, ICS 205-930, or GR 38032F, in single doses of 100 micrograms kg-1, i.a.). 5. Fast excitation showed marked tachyphylaxis and was antagonized by MDL 72222, ICS 205-930 or GR 38032F. It was unaffected by ketanserin (100 micrograms kg-1, i.a.). Delayed excitation was reduced or abolished by ketanserin but was unaffected by the 5-HT3-receptor antagonists. 6. Administration of MDL 72222, ICS 205-930 or GR 38032F caused short lasting (< 5 min) reductions in background activity from both types of unit recorded in arthritic rats, as well as in normal rats in which activity had increased following administration of 5-HT. Ketanserin caused similar reductions in background activity in chemosensitive units, but had no effect on mechanoreceptors. 7. At least two types of receptor are involved in the actions of 5-HT on articular sensory receptors with fine afferent fibres. Increased mechano-responsiveness involves a 5-HT3-receptor as does fast excitation. Delayed excitation probably involves a 5-HT2-receptor. Endogenous 5-HT appears not to play a crucial role in sensitization of high threshold mechanoreceptors in this model of chronic inflammation and arthritis, although its local release may potentiate the actions of other inflammatory mediators on sensory receptors in the ankle joint.
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PMID:The effects of 5-HT on articular sensory receptors in normal and arthritic rats. 207 87

1. The relative contributions of two classes of 5-hydroxytryptamine (5-HT) receptor (5-HT2 and 5-HT3) to the contractile action of 5-HT, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) were studied in the guinea-pig ileum longitudinal muscle-myenteric plexus strip (LMMP) preparation. Contractility studies were combined with an analysis of the effects of the three agonists on [3H]-acetylcholine ([3H]-ACh) release from preparations preincubated with [3H]-choline. 2. In contracting the LMMP, 5-HT was approximately one order of magnitude more active than 2-methyl-5-HT and alpha-methyl-5-HT, with relative activities for 5-HT: 2-methyl-5-HT: alpha-methyl-5-HT of 1.00: 0.13: 0.10. 3. Ketanserin (1 microM) was without effect on the concentration-response curves for concentration to 5-HT. 2-methyl-5-HT or alpha-methyl-5-HT, whilst ondansetron (GR38032F: 1 microM) produced a parallel rightward displacement of the upper part of the concentration-response curves to 5-HT and alpha-methyl-5-HT and of the entire curve to 2-methyl-5-HT. 4. In increasing the spontaneous release of [3H]-ACh from the LMMP, 5-HT was again approximately one order of magnitude more active than 2-methyl-5-HT and alpha-methyl-5-HT with relative activities for 5-HT: 2-methyl-5-HT: alpha-methyl-5-HT of 1.00: 0.19: 0.11. 5. Ondansetron (1 microM) greatly attenuated the increase in spontaneous [3H]-ACh release evoked by all three agonists. pKB estimates of 7.62 + 0.12 and 7.64 + 0.09 were obtained for ondansetron antagonism of 5-HT and 2-methyl-5-HT-evoked increases respectively. 6. These data suggest that the contractile action of 5-HT, 2-methyl-5-HT and a-methyl-5-HT in the guinea-pig ileum can, under these conditions, be accounted for largely in terms of 5-HT3 receptor activation. Estimates for pKB obtained with ondansetron are in accordance with those previously obtained from contractility studies in this preparation and these findings are discussed in terms of the postulated existence of subtypes of 5-HT3 receptors.
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PMID:An examination of the 5-HT3 receptor mediating contraction and evoked [3H]-acetylcholine release in the guinea-pig ileum. 215 Jan 79

5-Hydroxytryptamine (5-HT) contracts ring preparations of rabbit saphenous vein via direct and indirect components, the latter being compatible with a "tyramine-like" action at sympathetic nerve terminals. Here an attempt was made to establish the identity of the receptor mediating contraction directly, in terms of the currently accepted proposals (Bradley et al. 1986). Results with agonists suggested 5-HT1-like receptor activation: methylsergide behaved as a partial agonist with microcolar affinity and 5-HT effects were mimicked by 5-carboxamidotryptamine (5-CT) and GR43175. The agonist potency order was 5-CT greater than 5-HT greater than methysergide greater than or equal to GR43175, the same as that reported at the 5-HT1-like receptor in dog saphenous vein (Feniuk et al. 1985; Humphrey et al. 1988). Consistent with this, 5-HT effects were resistant to blockade by the selective 5-HT3 receptor antagonist MDL72222 (1.0 mumol/l). In contrast, methiothepin (0.01-0.3 mumol/l), ketanserin (0.3-30.0 mumol/l) and spiperone (0.3-30.0 mumol/l) each produced surmountable antagonism which, although competitive in nature only for methiothepin (pKB = 9.45 +/- 0.09, 17 d.f.), implied 5-HT2 receptor involvement. The possibility that these discrepancies resulted from mixed populations of 5-HT1-like and 5-HT2 receptors can be excluded because; 1). Ketanserin and spiperone blocked the actions of 5-HT and the selective 5-HT1-like receptor agonist GR43175 with equal facility and 2). Responses to all of the agonists studied were similarly antagonised by flesinoxan (pKB approximately 6.4), a simple competitive antagonist at the receptor in rabbit saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of the 5-HT receptor in rabbit saphenous vein exemplifies the problems of using exclusion criteria for receptor classification. 223 95

The effect of ketanserin (3 mg/kg i.v.) on the baroreceptor heart rate reflex and the Bezold-Jarisch reflex was examined in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the control situation (before ketanserin treatment), reflex bradycardia in response to phenylephrine (baroreflex) and phenyldiguanide (Bezold-Jarisch reflex) were impaired in SHR as compared with WKY, while reflex tachycardia in response to nitroprusside was similar in the two groups. However, after ketanserin administration in SHR, there was a reversal of the baroreflex-mediated tachycardia in response to nitroprusside into a bradycardic response. The nitroprusside-induced bradycardia was not caused by the release of 5-HT stimulating chemosensitive vagal afferents since the 5-HT3 receptor antagonist MDL 72222 did not block this response. In the same SHR, the Bezold-Jarisch reflex evoked by phenyldiguanide and the phenylephrine-induced bradycardia were potentiated by ketanserin. All the above effects of ketanserin were less evident in the WKY. Ketanserin did not alter vagal efferent function in anaesthetized SHR since it did not affect bradycardia induced by electrical stimulation of the vagus nerve. Therefore, it is suggested that ketanserin has sensitised cardiac vagal afferent mechanisms in SHR, which led to a normalization of reflex bradycardic function to a level normally observed in conscious normotensive WKY (i.e. prior to ketanserin treatment).
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PMID:The effect of ketanserin on cardiovascular reflexes in conscious normotensive and spontaneously hypertensive rats. 228 35

The effects of serotonin receptor antagonists with differential selectivity for the various classes of 5HT receptors (5HT1, 5HT2 and 5HT3) were tested for their effects on the response to aversive brain stimulation. Electrical stimulation was administered to the dorsal part of the periaqueductal gray matter (PAG), one of the main cerebral structures subserving negative reinforcement. Stimulation frequency thresholds for escape responses were recorded before and following administration of the compounds. Ketanserin (0.32-32 mg/kg IP), trazodone (1.0-22 mg/kg), pirenperone (0.032-1.0 mg/kg) and spiperone (0.1-0.2 mg/kg) dose-dependently increased stimulation frequency thresholds necessary to induce escape responses. Opposite effects were observed with mianserin (0.01-32 mg/kg) and metergoline (0.032-10 mg/kg) which decreased threshold for escape. ICS 205-930 (0.01-10 mg/kg), did not affect the stimulation frequency threshold for escape. Prazosin (0.1-22 mg/kg) did not specifically affect aversive brain stimulation. Haloperidol (0.02-1.0 mg/kg) increased the frequency threshold for escape responses but with some motoric side effects. These data show that the various types of 5HT receptors differentially contribute to the control of central aversive systems in rats. It is suggested that blockade of 5HT2 receptors suppresses the central aversive system, whereas blockade of some 5HT1 receptors enhances aversion and overcomes the 5HT2-mediated suppression. Blockade of 5HT3 receptors has no effects. Dopamine receptor blockade further contributes to the suppression of the central aversive system. The relevance of these findings to some pathophysiological mechanisms of anxiety and depressive disorders is discussed.
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PMID:Effects of serotonin receptor antagonists on PAG stimulation induced aversion: different contributions of 5HT1, 5HT2 and 5HT3 receptors. 249 46


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