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

Effect of Y-25130 on 5-hydroxytryptamine3 (5-HT3) receptors was investigated using the von Bezold-Jarisch effect (BJE) in anesthetized rats. Intravenous or intraduodenal administration of Y-25130 antagonized the BJE evoked by 5-HT and its effect was over 100 times more potent than that of metoclopramide. Y-25130 also completely blocked the BJE induced by 2-methyl-5-HT, a selective 5-HT3 receptor agonist. The BJE induced by 5-HT was not antagonized by spiperone, ketanserin, phenoxybenzamine, yohimbine and haloperidol, but antagonized by atropine. Atropine inhibited the bradycardia caused by electrical stimulation of the vagus nerve, but Y-25130 had no inhibitory effect. These results indicate that Y-25130 possesses a potent and selective 5-HT3 receptor antagonistic property.
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PMID:[Inhibition by Y-25130 of the von Bezold-Jarisch effect evoked by 5-HT or 2-methyl-5-HT in anesthetized rats]. 180 16

The effects of 5-hydroxytryptamine (5-HT), the 5-HT1-like receptor agonist 5-carboxamidotryptamine and the 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine were studied on circular muscle strips of the canine terminal ileum and ileocolonic junction. Serial administration of 5-HT or of 5-carboxamidotryptamine induced slow tonic contractions that at higher concentrations of 5-HT (10(-4)-3 x 10(-4] were preceded by an initial relaxation and a fast phasic contraction. The concentration-response curves to both agonists were competitively shifted to the right by the mixed 5-HT1/5-HT2 receptor antagonist methysergide. The initial relaxation and fast phasic contraction were inhibited by the 5-HT3 receptor antagonist ICS 205-930 and tetrodotoxin. Atropine blocked the fast phasic contraction, but enhanced the relaxation. During acetylcholine-induced contractions, 5-HT and 2-methyl-5-hydroxytryptamine (greater than or equal to 10(-5) M), but not 5-carboxamidotryptamine, evoked relaxations that were blocked by ICS 205-930 and tetrodotoxin, but not by adrenoceptor antagonists. Thus, in the canine terminal ileum and ileocolonic junction, 5-HT stimulates neuronal 5-HT3 receptors and excitatory 5-HT1-like receptors located on smooth muscle. Stimulation of the 5-HT3 receptors results in an acetylcholine-mediated contraction and a relaxation mediated by an as yet unknown nonadrenergic noncholinergic neurotransmitter.
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PMID:Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction. 238 90

The role of 5-HT3 receptors in the biphasic vasodilator response to serotonin (5-hydroxytryptamine; 5-HT) was investigated in the forearm of 7 young healthy volunteers (aged 22-32 years). Single dose infusions of 5-HT (1 ng/kg/min) and of acetylcholine (ACh, 500 ng/kg/min) were administered into the brachial artery. Subsequently combined infusions of 5-HT together with the selective 5-HT3 receptor antagonist ICS 205-930 (350 and 700 ng/kg/min), and ACh together with ICS 205-930 (700 ng/kg/min) were given. After a pause of at least 1 hour the single infusions of 5-HT and ACh were repeated. Subsequently, 5-HT and ACh were infused together with atropine (100 ng/kg/min). Forearm blood flow (FBF) was measured by R-wave triggered venous occlusion plethysmography. Heart rate (HR) and i.a. blood pressure (BP) were recorded semi-continuously. None of the drugs in the doses used did induce systemic hemodynamic effects. After an initial rapid transient increase in FBF of 316 +/- 55%, 5-HT elicited a persistent increase in FBF of 90 +/- 22% (mean +/- SEM, p less than 0.05 for both). ACh induced a monophasic vasodilatation of 475 +/- 123% (p less than 0.05). Both the initial transient and the persistent dilatator response to 5-HT were attenuated by ICS 205-930 350 ng/kg/min (p = 0.057, n = 5) and 700 ng/kg/min (p less than 0.05, n = 7). The highest dose of ICS 205-930 did not significantly influence the dilatator response to ACh. Atropine abolished the ACh induced vasodilatation (p less than 0.05), but did not influence the biphasic dilatator response to 5-HT. Thus the 5-HT induced biphasic vasodilatation was antagonized by ICS 205-930, indicating that this response was mediated by 5-HT3 receptor activation. The fact that atropine did not influence the vascular response to 5-HT suggests that 5-HT did not induce vascular relaxation indirectly by the release of ACh from cholinergic nerve endings.
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PMID:Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930. 318 2

The role of neuronal 5HT3 receptors in the vascular response induced by serotonin (5-hydroxytryptamine, 5HT) was investigated in seven healthy volunteers (aged 22-32 years). Single infusions of 5HT (1 ng/kg per min) and acetylcholine (500 ng/kg per min) were administered into the brachial artery in random order. Subsequently, 5HT and acetylcholine were administered together with the selective 5HT3 antagonist ICS 205-930 (700 ng/kg per min). After a pause of at least 1 h the single infusions of 5HT and acetylcholine were repeated. Finally, 5HT and acetylcholine were infused together with atropine (100 ng/kg per min). Forearm blood flow was measured by venous occlusion plethysmography. The heart rate and intra-arterial blood pressure were recorded semi-continuously. 5HT induced an initial transient increase in forearm blood flow (316 +/- 55%, mean +/- s.e.m., P less than 0.05), followed by persistent increase (90 +/- 22%, P less than 0.05). Acetylcholine elicited a monophasic vasodilation (delta forearm blood flow 475 +/- 123%, P less than 0.05). ICS 205-930 attenuated both the initial transient vasodilation and the persistent dilatory response to 5HT (P less than 0.05 for both), but did not significantly influence the vascular response to acetylcholine. Atropine abolished the dilator response to acetylcholine (P less than 0.05), but did not influence the biphasic vasodilation induced by 5HT. These results show that the biphasic vasodilation induced by 5HT was antagonized by ICS 205-930, indicating that this response was mediated by neuronal 5HT3-receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5HT3 receptor-mediated vasodilation in the human forearm. 324 Dec 16

It has been suggested that changes in brain 5-hydroxytryptamine3 receptor function may contribute to some behavior disorders, such as anxiety, schizophrenia and drug abuse. We are using the whole-cell version of the patch-clamp technique to study the function of 5-hydroxytryptamine3 channels in neurons freshly dissociated from rat nodose ganglion. In these cells, 5-hydroxytryptamine elicits an inward current over the concentration range of 0.25-100 microM (EC50 = 2.62 microM) by activating 5-hydroxytryptamine3 receptors. The muscarinic cholinergic antagonist atropine reduced the amplitude of 5-hydroxytryptamine activated inward current in a concentration-dependent manner. Other muscarinic antagonists, scopolamine, dexetimide, the M1 muscarinic receptor antagonist pirenzepine, the M2 receptor antagonist methoctramine and the M3 receptor antagonist 4-DAMP methiodide also inhibited 5-hydroxytryptamine-induced inward current. Atropine did not appear to change the reversal potential of this current. In the presence of 5 microM atropine, the concentration-response curve for 5-hydroxytryptamine current was shifted to the right in a parallel fashion. The EC50 value for 5-hydroxytryptamine was increased from 2.62 to 8.76 microM. Schild plots of increasing atropine and 5-hydroxytryptamine concentrations revealed a pA2 value of 5.74 for atropine (apparent KD = 1.8 microM). These observations suggest that atropine competitively antagonizes the activation of a receptor for the neurotransmitter serotonin, a novel action of muscarinic antagonists in the nervous system. This effect of atropine may contribute to the clinical symptoms seen in severe atropine intoxication.
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PMID:The effect of atropine on the activation of 5-hydroxytryptamine3 channels in rat nodose ganglion neurons. 753 5

In urethananesthetized ferrets, basal lower esophageal sphincter pressure (LESP) was unaffected by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist granisetron (0.5 mg/kg) or by greater splanchnic nerve section (GSX), but increased after bilateral vagotomy. Peripheral vagal nerve stimulation caused LES relaxation, often followed by a brief contraction and a prolonged inhibition of LESP. Close intra-arterial injection of 5-HT (5-100 micrograms) had a biphasic effect on LESP, with a brief drop followed by a prolonged increase. Granisetron (0.5 mg/kg i.v.) abolished the initial relaxation and revealed an earlier peak of excitation. This was not influenced by subsequent vagotomy and GSX. In a series of eight additional experiments (series 2), granisetron was given after vagotomy and GSX. In series 2, 5-HT-induced relaxation was unaffected by vagotomy but was significantly reduced after GSX and was further reduced after granisetron, indicating that 5-HT3 receptor mechanisms may lie on a sympathetic neural pathway. Vagotomy had no effect on the excitatory component. GSX had no effect on the amplitude of excitation, but reduced its latency. Granisetron had no further effect on excitation in series 2. In a separate series of 13 experiments (series 3), the excitatory component of the LES response to 5-HT was abolished by ketanserin (2.5 mg/kg i.v.) , after which only relaxation occurred. Both 5-HT2 and 5-HT3 antagonists in combination abolished all effects of 5-HT on LESP. Atropine (400 micrograms/kg i.v., n = 7) had no effect on 5-HT-induced LES responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of ferret lower esophageal sphincter to 5-hydroxytryptamine: pathways and receptor subtypes. 761 99

1. Experiments were carried out to characterize the receptors mediating the indirect excitatory response to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated trachea. 2. 5-HT caused concentration-dependent contractions of tracheal strips, and the resulting concentration-response curve was biphasic in nature. The first phase was obtained with agonist concentrations in the range of 0.01-3 nM and achieved a maximum which was 30% of the total 5-HT response, while the second phase was in the range 10 nM-1 microM. 3. Atropine (0.1 microM) and tetrodotoxin (TTX: 0.3 microM) significantly reduced both phases of the 5-HT curve. Morphine (10 microM), which can act to inhibit neuronal acetylcholine release, abolished the first phase and reduced the second phase. This suggests that the first phase is mainly neurogenic (cholinergic) in nature, while the second phase is in part neurogenic and in part due to direct activation of the effector cells. 4. The 5-HT2A receptor antagonist, ketanserin (0.01, 0.1 microM) markedly depressed the first phase and shifted the second phase to the right in a parallel manner, with some depression of the 5-HT response maximum. The less selective (5-HT1/5-HT2A) antagonist, methiothepin (0.1 microM) mimicked the action of ketanserin, albeit with less potency. Concomitant administration of ketanserin and methiothepin (each at 0.1 microM) produced an antagonism similar to that caused by ketanserin (0.1 microM) alone. 5. The 5-HT3 receptor antagonists, ondansetron (0.1 microM) and granisetron (0.01 microM) slightly but significantly inhibited the first phase of the 5-HT curve without altering the second phase. SDZ 205,557(0.3 MicroM), a 5-HT4 receptor antagonist, was ineffective.6. Our results suggest that neural 5-HT2A and, to a lesser extent, 5-HT3 receptor subtypes mediate the first phase of the 5-HT curve in the guinea-pig trachea. The second phase is mediated by 5-HT2Areceptors, which are probably located at both the neural and muscular level. No evidence for the participation of 5-HT1 receptors in the 5-HT response has been obtained.
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PMID:A pharmacological analysis of receptors mediating the excitatory response to 5-hydroxytryptamine in the guinea-pig isolated trachea. 792

The purpose of this study was to determine the effect of methysergide, ketanserin, granisetron, cisapride, and renzapride on serotonin (5-hydroxytryptamine-evoked short-circuit current in muscle and myenteric plexus-stripped pig jejunum using the Ussing chamber technique. Ketanserin, granisetron, cisapride, and renzapride all reduced the 5-hydroxytryptamine-induced increase in short-circuit current by about 50%. Combination of ketanserin and granisetron only reduced the 5-hydroxytryptamine-induced peak increase in short-circuit current by 25%. Cisapride caused a small concentration-dependent increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Ketanserin, granisetron, methysergide, and renzapride did not alter the basal short-circuit current. These results suggest that 5-hydroxytryptamine elicits an increase in short-circuit current by activating epithelial and submucosal 5-hydroxytryptamine2 and 5-hydroxytryptamine3 receptor subtypes. Furthermore, the short-circuit current-increasing effect of cisapride, is due to activation of at least muscarinic and nicotinic receptors.
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PMID:5-Hydroxytryptamine2 and 5-hydroxytryptamine3 receptors mediate serotonin-induced short-circuit current in pig jejunum. 798 49

The effect of EM523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2 alpha (PGF2 alpha). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2 alpha stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2 alpha for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM52 EM523 or motilin and partly inhibited PGF2 alpha-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2 alpha. Infusion of EM523 at 100 micrograms/kg/hr induced strong migrating contractions even when motility was depressed by dopamine infusion or laparotomy. Infusion of PGF2 alpha at 300 micrograms/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2 alpha-induced intestinal contractions.
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PMID:Comparison of the motor-stimulating action of EM523, an erythromycin derivative, and prostaglandin F2 alpha in conscious dogs. 828 32

We evaluated the inhibitory effects of YM060 [(R)-5-[(1-methyl-1H-indol- 3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride] and YM114 (KAE-393) [(R)-5-[(1-indolinyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole monohydrochloride] on the von Bezold-Jarisch reflex (BJR) induced by 2-methyl-5-HT, a selective serotonin (5-HT)3-receptor agonist; veratridine, which stimulates chemoreceptors and baroreceptors; and electrical stimulation of vagal efferent nerves in anesthetized rats. Results were compared with those of ondansetron and granisetron. 2-Methyl- 5-HT (5-160 micrograms/kg, i.v.) and veratridine (100-200 micrograms/kg, i.v.) dose-dependently decreased the heart rate (BJR). YM060, YM114, ondansetron and granisetron dose-dependently inhibited 2-methyl-5-HT (40 micrograms/kg, i.v.)-induced BJR, with ID50 values of 0.012, 0.060, 0.97 and 0.15 microgram/kg, i.v., respectively. Their 5-HT3 receptor blocking potencies against 2-methyl-5-HT-induced BJR were largely consistent with those against 5-HT-induced BJR. In contrast, higher doses (100 micrograms/kg, i.v.) of YM060, YM114, ondansetron and granisetron did not inhibit veratridine (150 micrograms/kg, i.v.)-induced BJR. Atropine (300 micrograms/kg, i.v.) abolished bradycardia induced by electrical stimulation of vagal efferent nerves, whereas YM060, YM114, ondansetron and granisetron had no effect at a dose of 1000 micrograms/kg, i.v. 5-HT (0.625-5.0 micrograms) injected into the left ventricle also caused a dose-dependent decrease in heart rate, an effect that was abolished by YM060 (0.1 microgram/kg, i.v.), atropine (100 micrograms/kg, i.v.) and vagotomy. These results suggest that YM060 and YM114 are highly potent and selective 5-HT3-receptor antagonists that do not affect veratridine- or electrical stimulation-induced bradycardia in anesthetized rats. They also suggest that 5-HT-induced BJR in anesthetized rats originates from 5-HT3 receptors located on the endings of vagal afferent nerves in the heart.
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PMID:Characteristics of inhibitory effects of serotonin (5-HT)3-receptor antagonists, YM060 and YM114 (KAE-393), on the von Bezold-Jarisch reflex induced by 2-Methyl-5-HT, veratridine and electrical stimulation of vagus nerves in anesthetized rats. 878 38


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