Angiotensin type 1A receptor regulates β-arrestin binding of the β2-adrenergic receptor via heterodimerization

Heterodimerization between angiotensin type 1A receptor (AT(1)R) and beta(2)-adrenergic receptor (beta(2)AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to beta-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on beta-arrestin coupling. We found that beta-arrestin binding of beta(2)AR is affected by activation of AT(1)Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between beta(2)AR and beta-arrestins, by prolonging the lifespan of beta(2)AR-induced (beta-arresting clusters at the plasma membrane. While candesartan, a conventional AT(1)R antagonist, had no effect on the (beta-arresting2 binding to beta(2)AR, TRV120023, a beta-arrestin biased agonist, enhanced the interaction. These findings reveal a new crosstalk mechanism between AT(1)R and beta(2)AR, and suggest that enhanced beta-arrestin2 binding to beta(2)AR can contribute to the pharmacological effects of biased AT(1)R agonists. (C) 2016 Published by Elsevier Ireland Ltd.