β 1 -adrenoceptor Arg389Gly polymorphism confers differential β-arrestin-binding tropism in cardiac myocytes.

Autor: McCrink KA; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA., Brill A; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA., Jafferjee M; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA., Valero TR; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA., Marrero C; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA., Rodriguez MM; MMR Healthcare, Boynton Beach, FL 33426, USA., Hale GM; Department of Pharmacy Practice, Nova Southeastern University College of Pharmacy, Palm Beach Gardens Campus, Palm Beach Gardens, FL 33410, USA., Lymperopoulos A; Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Fort Lauderdale, FL 33328, USA.
Jazyk: angličtina
Zdroj: Pharmacogenomics [Pharmacogenomics] 2016 Oct; Vol. 17 (15), pp. 1611-1620. Date of Electronic Publication: 2016 Sep 19.
DOI: 10.2217/pgs-2016-0094
Abstrakt: Aim: The β 1 -adrenergic receptor (AR) Arg389Gly polymorphism affects efficacy of its procontractile signaling in cardiomyocytes and carriers' responses to β-blockers. To identify molecular mechanisms underlying functional differences between Arg389 and Gly389 β 1 ARs, we examined their binding to β-arrestins (βarr-1 and -2), which mediate β 1 AR signaling, in neonatal rat ventricular myocytes.
Methods: We tested the β 1 AR-βarr interaction via β 1 AR immunoprecipitation followed by βarr immunoblotting.
Results: βarr1 binds both variants upon isoproterenol, carvedilol or metoprolol treatment in neonatal rat ventricular myocytes. Conversely, the potentially beneficial in the heart βarr2 only interacts with the Arg389 receptor in response to isoproterenol or carvedilol.
Conclusion: Arg389 confers unique βarr2-interacting tropism to the β 1 AR in cardiac myocytes, potentially underlying this variant's gain-of-function phenotype and better clinical responses to β-blockers.
Databáze: MEDLINE
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