Regulation of beta adrenoceptor-mediated myocardial contraction and calcium dynamics by the G protein-coupled estrogen receptor 1.

Autor: Whitcomb V; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States., Wauson E; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States., Christian D; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States., Clayton S; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States., Giles J; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States., Tran QK; Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, IA 50312, United States. Electronic address: kim.tran@dmu.edu.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2020 Jan; Vol. 171, pp. 113727. Date of Electronic Publication: 2019 Nov 21.
DOI: 10.1016/j.bcp.2019.113727
Abstrakt: The G protein-coupled estrogen receptor 1 (GPER) produces cardioprotective effects. However, the underlying mechanisms are not well understood. We aimed to investigate the role of GPER in β adrenoceptor-mediated cardiac contraction and myocardial signaling. In anesthetized animals, intrajugular administration of isoproterenol produces a rapid and sustained rise in left ventricular pressure (LVP) and increases ectopic contractions. Administration of the GPER agonist G-1 during the plateau phase of isoproterenol-induced LVP increase rapidly restores LVP to baseline levels and reduces the frequency of ectopic contractions. In freshly isolated cardiomyocytes, isoproterenol potentiates electrically induced peak currents of L-type Ca 2+ channels (LTCC) and increases the potential sensitivity of their inactivation. Coadministration of G-1 prevents isoproterenol-induced potentiation of peak LTCC currents and makes channels more sensitive to being inactivated compared to isoproterenol alone. Isoproterenol treatment of cardiomyocytes without electrical stimulation triggers slow-rising Ca 2+ signals that are inhibited by the β 1 AR antagonist metoprolol but not by β 2 AR antagonist ICI-118551. G-1 pretreatment dose-dependently suppresses isoproterenol-induced total Ca 2+ signals and the amplitude and frequency of the intrinsic Ca 2+ oscillatory deflections. Pretreatment with the GPER antagonist G-36 produces opposite effects, dose-dependently increasing these signals. ISO promotes robust phosphorylation of Ca v 1.2 channels at Ser1928. G-1 pretreatment inhibits isoproterenol-stimulated phosphorylation of Ca v 1.2 at Ser1928, while G-36 pretreatment enhances this signal. Our data indicate that GPER functions as an intrinsic component of β 1 AR signaling to moderate myocardial Ca 2+ dynamics and contraction.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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