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

AIM

The β-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 βARs, we examined their binding to β-arrestins (βarr-1 and -2), which mediate βAR signaling, in neonatal rat ventricular myocytes.

METHODS

We tested the βAR-βarr interaction via βAR 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 βAR in cardiac myocytes, potentially underlying this variant's gain-of-function phenotype and better clinical responses to β-blockers.