Comparison of the positive chronotropic response to 5-hydroxytryptamine with beta-adrenoceptor agonists on the guinea pig atria in vitro.

The positive chronotropic response to 5-hydroxytryptamine (5-HT) in the isolated guinea pig atria was analyzed. The response to 5-HT was compared with the effects of 5-carboxamidotryptamine (5-CT), 8-dihydroxydiphenylaminotetralin (8-OH-DPAT), isoprenaline, prenalterol, dobutamine, salbutamol, and norepinephrine (NE). In comparison to isoprenaline 5-HT, prenalterol, dobutamine, salbutamol, and NE acted as partial agonists, whereas 5-CT and 8-OH-DPAT did not produce a response. The response to 5-HT was unaffected by 1 microM methysergide, metergoline, ketanserin, MDL 72222, ICS 205-930, phentolamine, or 0.1 mM hexamethonium. However, the beta-adrenoceptor antagonists, pindolol and atenolol, antagonized the response to 5-HT in a noncompetitive manner. The response to 5-HT was unaffected by reserpinization or beta-adrenoceptor desensitization. Thus, the positive chronotropic response to 5-HT in this preparation is a direct effect but is not mediated by 5-HT1-like, 5-HT2, or 5-HT3 receptors.