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. Talipexole showed moderate displacement activity of 3H-GR 65630 binding to 5-HT3 receptors in both rat cortical and intestinal membrane fractions with Ki values of 0.35 microM and 0.22 microM, respectively. 2. Bromocriptine failed to displace the binding activity in either experimental system even at a concentration of 10 microM. 3. Both talipexole and tropisetron were found to significantly inhibit 5-HT3 receptor-mediated effects of 5-HT in isolated guinea-pig ileum or atrium; however, the effect of talipexole was weaker than that of tropisetron. 4. Bromocriptine, in contrast, had no antagonistic effects on 5-HT3 receptor-mediated activity in guinea-pig ileum or atrium. 5. It was concluded that talipexole might act as an antagonist on 5-HT3 receptors in both brain and intestinal tissues.
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PMID:5-HT3 receptor blocking properties of the antiparkinsonian agent, talipexole. 884 79

The involvement of abdominal afferent vagal activity and serotonergic mechanisms were examined following intravenous administration of talipexole, a dopamine D2 receptor agonist used for treatment of Parkinson's disease, in anesthetized rats. Intravenous administration of dopamine receptor agonists including D1/D2 components increased the spontaneous firing of afferent vagal neurons as did 2-methyl-5-hydroxytryptamine. Both talipexole (0.25-1.0 mg/kg) and bromocriptine (1.0-10.0 mg/kg) increased vagal nerve activity in a dose-dependent manner, and the effect of 10 mg/kg of bromocriptine was significantly greater than that noted with 1.0 mg/kg of talipexole. Increasing vagal firing induced by talipexole was prevented by pretreatment with granisetron, but not with metoclopramide or by spinal section, indicating that afferent vagal firing was mediated via stimulation of the 5-HT3 receptors on the neurons and secondarily caused by stimulation of dopamine receptors. On the other hand, bromocriptine at 5 mg/kg increased 5-HIAA concentration in the ileum, and serotonin turnover (5-HIAA/5-HT) was increased approximately 4-fold when compared to the vehicle group. Bromocriptine also increased the activities of tryptophan hydroxylase and monoamine oxidase. Talipexole at 0.5 mg/kg did not affect ileal 5-HT metabolism and the enzymatic activities. These findings suggest that dopamine receptor agonists may induce changes in abdominal afferent vagal activity and ileal 5-HT metabolism similar to those observed with emetic compounds, and that talipexole has a much smaller influence on serotonin-mediated responses than does bromocriptine with equipotent antiparkinsonian doses. One of the possible reason why talipexole showed fewer emetic side effects in patients with Parkinson's disease may be that the emetic responses triggered by D2 receptor stimulation may secondarily cause an increase of abdominal afferent vagal activity, which may be weakened by the 5-HT3 receptor antagonistic property of talipexole.
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PMID:Effects of talipexole on emesis-related changes in abdominal afferent vagal activity and ileal serotonin metabolism in rats. 905 50

In order to elucidate the role of emetic action, the effects of talipexole and bromocriptine, two antiparkinsonian dopamine receptor agonists, on serotonin (5-HT) release from enterochromaffin (EC) cells were studied by measuring 5-HT concentrations in the perfusate of the isolated rat ileum. Bromocriptine (10(-8)-10(-6) M), which exerts agonistic effects on D1 and D2 receptors, increased 5-HT release in a concentration-dependent manner. No significant increase in 5-HT release was seen after addition of talipexole, which selectively stimulates D2 receptors and blocks 5-HT3 receptors, even at 10(-6) M. The increase in 5-HT release caused by bromocriptine at 10(-6) M was inhibited by administration of 10(-6) M of D1 receptor antagonist SCH 23390, D2 receptor antagonist spiperone, 5-HT3 receptor antagonist granisetron or tetrodotoxin (TTX). These results showed the involvement of both dopaminergic and serotonergic mechanisms in the 5-HT release from EC cells following the administration of dopamine receptor agonists. Bromocriptine might induce 5-HT release by stimulating D1, D2 and 5-HT3 receptors and depolarizing neurons in the ileum. On the other hand, talipexole might weaken 5-HT release from EC cells elicited by D2 receptor stimulation with its 5-HT3 receptor blocking property. It is suggested that the emetic effect of dopamine receptor agonists involves the peripheral gastrointestinal tract as their site of action.
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PMID:Differential effects of talipexole and bromocriptine on serotonin release from rat intestinal tissues--an in vitro study of the emetic response of antiparkinsonian dopamine agonists. 1060 73