Different Regulation of ERK1/2 Activation by β-Adrenergic Receptor Subtypes in Adult Mouse Cardiomyocytes

Abstract

Background. Increasing evidence suggests that stimulation of β-adrenergic receptor (βAR) activates mitogen-activated protein kinases (MAPKs), particularly extracellular signal-regulated kinase (ERK1/2) which is involved in the regulation of a multitude of cellular processes. However, the subtype-specific effects of βAR stimulation on MAPKs remain to be elucidated. Aims. In the present study, we determined whether β 1AR and β 2AR differ in regulating ERK1/2 activation in the myocardium. Methods. To avoid complicated interactions between βAR subtypes, we separately expressed either β 1AR or β 2AR using adenoviral gene transfer in adult mouse cardiac myocytes from β 1β 2 double knockout mice. Results. Stimulation of β 1AR by isoproterenol markedly increased ERK phosphorylation and activity by 2.1-fold in a time-dependent manner. In contrast, stimulation of β 2AR slightly decreased ERK activation. Furthermore, pretreatment of cells with pertussis toxin to disrupt Gi function did not affect the inhibitory effect of β 2AR on ERK1/2. Conclusions. We have shown that stimulation of cardiac βAR subtypes differentially regulates ERK activation in adult mouse cardiomyocytes.