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  • Title: Receptor mechanisms involved in the 5-HT-induced inotropic action in the rat isolated atrium.
    Author: Läer S, Remmers F, Scholz H, Stein B, Müller FU, Neumann J.
    Journal: Br J Pharmacol; 1998 Mar; 123(6):1182-8. PubMed ID: 9559903.
    Abstract:
    1. The effects of 5-hydroxytryptamine (5-HT) in rat cardiac preparations were studied. 5-HT up to 10 microM 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 microM and attained its maximum at 10 microM (312+/-50% of predrug value, n=8). 2. 5-HT 10 microM 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 microM and 15 microM, respectively. 4. The selective 5-HT4 receptor antagonists GR 125487 (10 nM and 1 microM) and SB 203186 (1 microM) 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 microM) 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.
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