Cardiac overexpression of the human 5-HT4 receptor in mice

American Journal of Physiology. Heart and Circulatory Physiology
Ulrich GergsJ Neumann

Abstract

Serotonin (5-HT) exerts pleiotropic effects in the human cardiovascular system. Some of the effects are thought to be mediated via 5-HT(4) receptors, which are expressed in the human atrium and in ventricular tissue. However, a true animal model to study these receptors in more detail has been hitherto lacking. Therefore, we generated, for the first time, a transgenic (TG) mouse with cardiac myocyte-specific expression of the human 5-HT(4) receptor. RT-PCR and immunohistochemistry revealed expression of the receptor at the mRNA and protein levels. Stimulation of isolated cardiac preparations by isoproterenol increased phospholamban phosphorylation at Ser(16) and Thr(17) sites. 5-HT increased phosphorylation only in TG mice but not in wild-type (WT) mice. Furthermore, 5-HT increased contractility in isolated perfused hearts from TG mice but not WT mice. These effects of 5-HT could be blocked by the 5-HT(4) receptor-selective antagonist GR-125487. An intravenous infusion of 5-HT increased left ventricular contractility in TG mice but not in WT mice. Similarly, the increase in contractility by 5-HT in isolated cardiomyocytes from TG mice was accompanied by and probably mediated through an increase in L-type Ca(2+) channel current ...Continue Reading

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Citations

Jan 12, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Ulrich GergsJoachim Neumann
Jan 10, 2013·Acta Physiologica·A Bogdanova
Mar 1, 2012·Molecular and Cellular Biochemistry·Klaus PönickeJoachim Neumann
Feb 8, 2019·The Journal of Pharmacology and Experimental Therapeutics·U GergsJ Neumann
Sep 20, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Bernardo DolceCristina E Molina
Aug 4, 2016·Acta Physiologica·U GergsJ Neumann
Jul 10, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Ulrich GergsJoachim Neumann
Jun 28, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·Nicolas KellerUlrich Gergs
Apr 25, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Joachim NeumannUlrich Gergs
Oct 18, 2019·Frontiers in Pharmacology·Peter BoknikJoachim Neumann
Sep 17, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Ulrich GergsJoachim Neumann
Feb 13, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Joachim NeumannUlrich Gergs
May 29, 2021·Frontiers in Pharmacology·Joachim NeumannUlrich Gergs
May 29, 2021·European Journal of Pharmacology·Ulrich GergsJoachim Neumann
Sep 19, 2021·The Journal of Pharmacology and Experimental Therapeutics·Ulrich GergsJoachim Neumann

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