Re-examination for pharmacological properties of serotonin-induced tachycardia in isolated guinea-pig atrium.
In the presence of 10(-6) M atropine, 5-HT induced a positive chronotropic and inotropic effect in isolated guinea-pig atrium preparation. Both propranolol, a beta-adrenoceptor blocker, and imipramine, a 5-HT uptake inhibitor, did not affect the response induced by 5-HT, indicating that a tyramine-like mechanism is not involved. The positive chronotropic effect of 5-HT was mimicked by several 5-HT3 receptor agonists. N omega-Methyl-5-HT, reported to have a high affinity for 5-HT1B recognition sites, was found to act as a 5-HT3 receptor agonist with higher efficacy. The other 5-HT receptor agonists tested did not produced any responses. The positive chronotropic effect of 5-HT was inhibited by various 5-HT3 receptor antagonists, such as tropisetron, granisetron, ondansetron, cisapride and zacopride, but it was unaffected by various 5-HT receptor antagonists which are not selective for 5-HT3 receptor. Thus, the positive chronotropic response to 5-HT is a direct effect, and it was suggested to be mediated by 5-HT3 receptor subtype with rather an atypical profile.
Nishio
H
H
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Fujii
A
A
Nakata
Y
Y
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008559:Memantine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D018691:Excitatory Amino Acid Antagonists; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011433:Propranolol; D007099:Imipramine; D008559:Memantine