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)

1. The effects of microinjections (100 nl) into the dorsal motor vagal nucleus of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the 5-HT2 receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), the 5-HT3 receptor agonist phenylbiguanide (PBG), the alpha 2-adrenoceptor agonist clonidine and the excitatory amino acid glutamate on heart rate, blood pressure, tracheal pressure and phrenic nerve activity were investigated in atenolol-pretreated rats anaesthetized with sodium pentobarbitone. 2. Microinjections of glutamate (2.5 nmol) caused decreases in blood pressure, heart rate and phrenic nerve activity. In contrast, microinjections of 5-HT (1.2 nmol), 8-OH-DPAT (1.2 nmol) and flesinoxan (1.3 nmol) all caused a bradycardia but had no effect on blood pressure. In addition, 8-OH-DPAT and flesinoxan caused an increase in phrenic nerve activity. 3. Microinjections of DOI, PBG and clonidine had no significant effect on any of the variables recorded. None of the drugs used had any significant effect on tracheal pressure. 4. These results support the hypothesis that activation of 5-HT1A receptors causes excitation of cardiac vagal motoneurones and suggest that these receptors are also important in the control of central respiratory drive.
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PMID:Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. 179 13

In 16-week-old Sprague-Dawley rats lightly anesthetized with pentobarbital, 5-HT (3-96 micrograms/kg, i.v.; n = 6) produced distinct pseudaffective responses and a dose-dependent (slope = 17.2 +/- 6.8 s/log10 dose) inhibition of the tail-flick (TF) reflex (ED50 = 32.6 +/- 9.2 micrograms/kg). In the same rats, a 1:1 combination of alpha-methyl 5-HT (a 5-HT2, receptor selective agonist) and 2-methyl 5-HT (a 5-HT3 receptor selective agonist) (3-192 micrograms/kg, i.v.), produced the same profile of pseudaffective responses and also resulted in a dose-dependent (slope = 34.0 +/- 7.0 s/log10 dose) inhibition of the TF reflex (ED50 = 88.4 +/- 20.5 micrograms/kg). In contrast, administration of alpha-methyl 5-HT (3-192 micrograms/kg, i.v.) or 2-methyl 5-HT (3-192 micrograms/kg, i.v.) alone did not produce any pseudaffective responses or any change in TF latency from baseline. In conscious 16-week-old male Sprague-Dawley rats, administration of 5-HT (48 micrograms/kg, i.v.; n = 5), or a 1:1 combination of alpha-methyl 5-HT and 2-methyl 5-HT (total dose = 120 micrograms/kg, i.v.; n = 5), resulted in a passive avoidance behavior assessed in a step-down paradigm (slopes = 139.7 +/- 58.2 and 154.9 +/- 63.9 s/trial, respectively), and the same profile of distinct pseudaffective responses exhibited by the lightly pentobarbital-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The peripheral nociceptive actions of intravenously administered 5-HT in the rat requires dual activation of both 5-HT2 and 5-HT3 receptor subtypes. 179 50

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

Ligands of various chemical classes (e.g., indoles, indazoles, benzamides, carbazoles, and quinolines) have demonstrated high affinity for the 5-HT3 receptor in radiolabeled ligand-binding studies, and have shown 5-HT3 receptor antagonistic activity in functional assays which utilize the excitatory effects of 5-HT on enteric neurons and autonomic afferents. Several 5-HT3 antagonists are currently being evaluated for potential use in the treatment of migraine, schizophrenia, and anxiety, and a few have already demonstrated high efficacy as antiemetics in cancer chemotherapy. The purpose of this presentation is to highlight the significant structure-affinity relationships (SAFIR) and common geometrical features among 5-HT3 receptor ligands, and to describe the three-dimensional pharmacophore for the 5-HT3 recognition site derived from computational techniques. The chemical template containing the recognition elements (functional groups) for the 5-HT3 receptor are: an aromatic or heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center, interrelated by well-defined distances. Two "binding shapes" or "active shapes" for 5-HT3 ligands have been identified from detailed conformational analyses.
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PMID:Molecular modeling of 5-HT3 receptor ligands. 181 57

1. Acetylcholine (ACh) release from the cerebral cortex of freely moving guinea-pigs, implanted with epidural cups, was studied. 2. A single dose of chlorimipramine (Cl-Imip, 10 mg kg-1, s.c.), reduced the cortical ACh release both in normal and in chronically (10 mg kg-1 daily, s.c., for 14 days) Cl-Imip-treated guinea-pigs; the 5-HT3 antagonist MDL 72222 (1 mg kg-1, s.c.) antagonized this effect. 3. A single dose of Cl-Imip significantly reduced the effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylaminotetralin) (8-OH-DPAT, 0.1 mg kg-1, s.c.), which nearly doubled the cortical ACh release in control animals. MDL 72222 restored to normal the response to 8-OH-DPAT reduced by the anti-depressant. 4. A single dose of Cl-Imip did not change the inhibitory, MDL 72222-sensitive, effect induced by the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT, 500 micrograms, i.c.v.). 5. In chronically Cl-Imip-treated guinea-pigs, the facilitatory effect of 8-OH-DPAT was no longer present, while the inhibitory, MDL 72222-sensitive, effect of 2-methyl-5-HT was maintained. 6. These results indicate that the 5-HT1A receptor-mediated increase in ACh release is reduced by prolonged Cl-Imip treatment, while the 5-HT3 receptor-mediated inhibition of ACh release is unaffected. The relevance of these findings to the antidepressant mechanism of Cl-Imip is discussed.
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PMID:Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from the cerebral cortex of freely moving guinea-pigs. 183 Feb 35

Recent data have supported a role for serotonin (5-HT) in the self-administration of cocaine by laboratory rats. More specifically, it has been suggested that 5-HT3 receptor antagonists may be useful in the treatment of drug abuse. To assess this possibility, we compared the effects of the 5-HT3 antagonist, GR38032F, with the dopamine D2 receptor blocker, haloperidol, on the intravenous self-administration of cocaine (0.5 mg/kg/infusion) in rats. The serotonin antagonist (0.01, 0.1 or 1.0 mg/kg, IP) failed to alter self-administration (0.5 mg/kg/infusion). In contrast, haloperidol (0.125 mg/kg, IP) increased responding for cocaine (0.5 mg/kg/infusion), and shifted the dose-response curve for cocaine self-administration to the right. These data fail to support a role for the serotonin 5-HT3 receptor system in the reinforcing properties of this psychostimulant. Rather, the 5-HT1 or 5-HT2 receptors may be the critical subtype.
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PMID:GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats. 183 79

The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca(2+)-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 muM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 muM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 muM, respectively. The effect of 5-HT on Ca(2+)-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.
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PMID:Effect of cocaine and 5-HT3 receptor antagonists on 5-HT-induced [3H]dopamine release from rat striatal synaptosomes. 183 40

The contractile effect of serotonin (5-HT) on rabbit ophthalmic artery was studied. In a solution containing 20 mM K+ 5-HT induced a biphasic dose-response curve (DRC) in intact arteries. At normal extracellular K+ concentration ([K+]o), only high concentrations of 5-HT (greater than or equal to 1 microM) were able to induce contraction. In endothelium-denuded arteries 5-HT induced a DRC at normal [K+]o, which resembled that in intact arteries at 20 mM [K+]o. The high-potency portion of the 5-HT DRC was inhibited only by metitepine, whereas the low-potency portion was blocked by metitepine, methysergide, spiperone, and ketanserin, indicating that in this preparation the 5-HT1 receptor subtypes are more sensitive to 5-HT than the 5-HT2 receptor subtypes. Cyanopindolol had no effect on 5-HT-induced contraction. 8-Hydroxy-2-(di-n-propylamino)tetralin gave a contraction at high concentrations (greater than or equal to 0.1 microM), which was not blocked by cyanopindolol. The contractile response to 5-methoxytryptamine was similar to that for 5-HT. The results indicate that the 5-HT1 receptors of the ophthalmic artery belong either to 1C or 1D subtypes. 2-Methylserotonin, an agonist for 5-HT3 receptor, had no contractile effect on rabbit ophthalmic artery. The effect of prior exposure to 5-HT on norepinephrine (NE)-induced contraction was also studied. In intact arteries prior exposure to a low 5-HT concentration (10 nM) induced attenuation and prior exposure to a high 5-HT concentration (1 microM) gave potentiation of the NE-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic responses in rabbit ophthalmic artery: a pharmacological characterization. 183 10

The novel, naphthylpiperazine 5-HT1A agonist, S 14671 (4-[(thenoyl-2)aminoethyl]-1-(7-methoxynaphtylpiperazine], displayed very high affinity for 5-HT1A binding sites (pKi = 9.3) as compared to the serotonin (5-HT)1A agonists, 8-OH-DPAT (9.2) and (+)-flesinoxan (8.7) and the 5-HT1A partial agonists, buspirone (7.9) and BMY 7378 (8.8). In vivo, S 14671 induced the typical 5-HT1A agonist-induced responses of hypothermia and spontaneous tail-flicks at doses as low as greater than or equal to 5 micrograms/kg s.c. and greater than or equal to 40 micrograms/kg s.c., respectively. In each test, it was about 10-fold more potent than 8-OH-DPAT and 100-fold more potent than (+)-flesinoxan and buspirone. The actions of S 14671 could be blocked by BMY 7378 and the 5-HT1A receptor antagonist, (-)-alprenolol, but not by the 5-HT1C/2 receptor antagonist, ritanserin, nor the 5-HT3 receptor antagonist, ICS 205930. Thus, S 14671 is a novel 5-HT1A ligand of high efficacy and exceptional in vivo potency.
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PMID:S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency. 183 84

Excitatory response to 5-hydroxytryptamine was recorded from the external carotid nerve, a branch of the superior cervical ganglia, in anesthetized rats using an electrophysiological technique. Bolus intravenous injection of 5-HT (1.5625-50 micrograms/kg) evoked a rapid and dose-dependent excitation of external carotid nerve activity. This response was blocked by a selective 5-HT3-receptor antagonist, GR38032F (10 micrograms/kg). A 5-HT3 receptor agonist, 2-methyl-5-HT (3.125-50 micrograms/kg), also produced a rapid and dose-dependent excitation of external carotid nerve activity. GR38032F (10 micrograms/kg) caused a significant rightward shift in the 2-methyl-5-HT dose-response curve. These results suggest that the 5-HT-induced excitatory response of ECNA might be mediated via a 5-HT3 receptor.
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PMID:Effect of 5-hydroxytryptamine on external carotid nerve activity and its blockade by GR38032F in anesthetized rats. 183 26


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