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

Abstract

1. 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).

2. 5-HT 10 μM 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 μM and 15 μM, respectively.

4. 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.

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-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-HT_2A receptors and not through 5-HT₄ receptors.

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