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 μ 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 μ M and attained its maximum at 10 μ M (312±50% of predrug value, n =8). 2 5‐HT 10 μ 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 μ M and 15 μ M , respectively. 4 The selective 5‐HT 4 receptor antagonists GR 125487 (10 n M and 1 μ M ) and SB 203186 (1 μ M ) did not attenuate the positive inotropic effect of 5‐HT in rat left atria. In contrast, the 5‐HT 2 receptor antagonist ketanserin (5 n M , 50 n M , 1 μ 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‐HT 2A receptor in rat atria and ventricles, while expression of the 5‐HT 4 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‐HT 2A receptors and not through 5‐HT 4 receptors.British Journal of Pharmacology (1998) 123 , 1182–1188; doi: 10.1038/sj.bjp.0701702