Receptor mechanisms involved in the 5-HT-induced inotropic action in the rat isolated atrium

1 The effects of 5-hydroxytryptamine (5-HT) in rat cardiac preparations were studied. 5-HT up to 10 mu M failed to affect contractility in papillary muscles. However, in electrically driven (1 Hz) left atria 5-HT exerted a positive inotropic effect that started at 1 mu M and attained its maximum at 10 mu M (312+/-50% of predrug value, n=8). 2 5-HT 10 mu M stimulated the content of inositol-1,4,5-trisphosphate but not of cyclic AMP in rat left atria. 3 Plasma and serum levels of 5-HT amounted to about 0.3 mu M and 15 mu M, respectively. 4 The selective 5-HT, receptor antagonists GR 125487 (10 nM and 1 mu M) and SB 203186 (1 mu M) did not attenuate the positive inotropic effect of 5-HT in rat left atria. In contrast, the 5-HT2 receptor antagonist ketanserin (5 nM, 50 nM, 1 mu M) resulted in a concentration-dependent diminution of the positive inotropic effect of 5-HT in rat left atria. 5 Reverse transcriptase polymerase chain reaction with specific primers detected mRNA of the 5-HT2A receptor in rat atria and ventricles, while expression of the 5-HT4 receptor was confined to atria. 6 It is suggested that the positive inotropic effect of 5-HT in electrically driven rat left atria is mediated by ketanserin-sensitive 5-HT2A receptors and not through 5-HT4 receptors.