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

The effects of 5‐hydroxytryptamine (5‐HT) in rat cardiac preparations were studied. 5‐HT up to 10 μM 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 μM and attained its maximum at 10 μM (312±50% of predrug value, n=8). 5‐HT 10 μM stimulated the content of inositol‐1,4,5‐trisphosphate but not of cyclic AMP in rat left atria. Plasma and serum levels of 5‐HT amounted to about 0.3 μM and 15 μM, respectively. The selective 5‐HT4 receptor antagonists GR 125487 (10 nM and 1 μM) and SB 203186 (1 μM) 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 μM) resulted in a concentration‐dependent diminution of the positive inotropic effect of 5‐HT in rat left atria. 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. 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. British Journal of Pharmacology (1998) 123, 1182–1188; doi:10.1038/sj.bjp.0701702