Functional interaction of H 2 -receptors and 5HT 4 -receptors in atrial tissues isolated from double transgenic mice and from human patients.

Autor: Neumann J; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany. Joachim.neumann@medizin.uni-halle.de., Schwarzer D; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany., Fehse C; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany., Schwarz R; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany., Marusakova M; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia., Kirchhefer U; Institut Für Pharmakologie Und Toxikologie, Westfälische Wilhelms-Universität, Medizinische FakultätDomagkstr. 12, 48149, Münster, Germany., Hofmann B; Cardiac Surgery, Martin-Luther-Universität Halle-Wittenberg, Medizinische Fakultät, 06097, Halle, Germany., Gergs U; Institut Für Pharmakologie Und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische FakultätMagdeburger Str. 4, 06112, Halle, Germany.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2021 Dec; Vol. 394 (12), pp. 2401-2418. Date of Electronic Publication: 2021 Sep 25.
DOI: 10.1007/s00210-021-02145-8
Abstrakt: In the past, we generated transgenic mice that overexpress the human histamine 2 (H 2 )-receptor (H 2 -TG) or that overexpress the human serotonin 4 (5-HT 4 )-receptor (5-HT 4 -TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable interaction between these receptors in the mouse heart as a model for the human heart. When in left atria, initially, force of contraction was elevated maximally with 1 µM serotonin, and subsequently, histamine was cumulatively applied; a biphasic effect of histamine was noted: the force of contraction initially decreased, maximally at 10 nM histamine, and thereafter, the force of contraction increased again at 1 µM histamine. Notably, functional interaction between 5-HT and histamine was also identified in isolated electrically stimulated trabeculae carneae from human right atrium (obtained during cardiac surgery). These functional and biochemical data together are consistent with a joint overexpression of inotropically active H 2 -receptors and 5-HT 4 -receptors in the same mouse heart. We also describe an antagonistic interaction on the force of contraction of both receptors in the mouse atrium (DT) and in the human atrial muscle strips. We speculate that via this interaction, histamine might act as a "brake" on the cardiac actions of 5-HT via inhibitory GTP-binding proteins acting on the activity of adenylyl cyclase.
(© 2021. The Author(s).)
Databáze: MEDLINE
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