Receptor mechanisms involved in the 5‐HT‐induced inotropic action in the rat isolated atrium
1998; Wiley; Volume: 123; Issue: 6 Linguagem: Inglês
10.1038/sj.bjp.0701702
ISSN1476-5381
AutoresStephanie Läer, Freerk Ole Remmers, Hasso Scholz, Birgitt Stein, Frank U. Müller, Joachim Neumann,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoThe 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). 5‐HT 10 μ M 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 μ M and 15 μ M , respectively. 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. 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. 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
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