Abstract
BACKGROUND Increasing evidence suggests that stimulation of beta-adrenergic receptor (betaAR) 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 betaAR stimulation on MAPKs remain to be elucidated. AIMS In the present study, we determined whether beta(1)AR and beta(2)AR differ in regulating ERK1/2 activation in the myocardium. METHODS To avoid complicated interactions between betaAR subtypes, we separately expressed either beta(1)AR or beta(2)AR using adenoviral gene transfer in adult mouse cardiac myocytes from beta(1)beta(2) double knockout mice. RESULTS Stimulation of beta(1)AR by isoproterenol markedly increased ERK phosphorylation and activity by 2.1-fold in a time-dependent manner. In contrast, stimulation of beta(2)AR slightly decreased ERK activation. Furthermore, pretreatment of cells with pertussis toxin to disrupt Gi function did not affect the inhibitory effect of beta(2)AR on ERK1/2. CONCLUSIONS We have shown that stimulation of cardiac betaAR subtypes differentially regulates ERK activation in adult mouse cardiomyocytes.
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