Opposing effects of beta(1)- and beta(2)-adrenergic receptors on cardiac myocyte apoptosis - Role of a pertussis toxin-sensitive G proteins

Background-beta-Adrenergic receptor (P-AR) stimulation increases apoptosis in adult rat cardiac (ventricular) myocytes (ARVMs) via activation of adeny lyl cyclase. beta(2)-ARs may couple to a G(1)-mediated signaling pathway th at can oppose the actions of adenylyl cyclase. Methods and Results-In ARVMs, beta-AR stimulation for 24 hours increased th e number of apoptotic cells as measured by flow cytometry. beta-AR-stimulat ed apoptosis was abolished by the beta(1)-AR-selective antagonist CGP 20712 A (P<0.05 versus beta-AR stimulation alone) but was potentiated by the beta (2)-AR-selective antagonist ICI 118,551 (P<0.05 versus beta-AR stimulation alone). The muscarinic agonist carbachol also prevented beta-AR-stimulated apoptosis (P<0.05 versus PAR stimulation alone), whereas pertussis toxin po tentiated the apoptotic action of beta-AR stimulation (P<0.05 versus beta-A R stimulation alone) and prevented the antiapoptotic action of carbachol. Conclusions-In ARVMs, stimulation of beta(1)-ARs increases apoptosis via a cAMP-dependent mechanism, whereas stimulation of beta(2)-ARs inhibits apopt osis via a G(1)-coupled pathway, These findings have implications for the p athophysiology and treatment of myocardial failure.