Opposing effects of beta(1)- and beta(2)-adrenergic receptors on cardiac myocyte apoptosis : role of a pertussis toxin-sensitive G protein.

Communal C, Singh K, Sawyer DB, Colucci WS
Circulation. 1999 100 (22): 2210-2

PMID: 10577992 · DOI:10.1161/01.cir.100.22.2210

BACKGROUND - beta-Adrenergic receptor (beta-AR) stimulation increases apoptosis in adult rat cardiac (ventricular) myocytes (ARVMs) via activation of adenylyl cyclase. beta(2)-ARs may couple to a G(i)-mediated signaling pathway that can oppose the actions of adenylyl cyclase.

METHODS AND RESULTS - In ARVMs, beta-AR stimulation for 24 hours increased the number of apoptotic cells as measured by flow cytometry. beta-AR-stimulated apoptosis was abolished by the beta(1)-AR-selective antagonist CGP 20712A (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 beta-AR stimulation alone), whereas pertussis toxin potentiated the apoptotic action of beta-AR stimulation (P<0.05 versus beta-AR 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 apoptosis via a G(i)-coupled pathway. These findings have implications for the pathophysiology and treatment of myocardial failure.

MeSH Terms (24)

Adenylate Cyclase Toxin Adrenergic beta-Agonists Adrenergic beta-Antagonists Animals Apoptosis Carbachol Cardiotonic Agents Cyclic AMP GTP-Binding Protein alpha Subunits, Gi-Go Heart Imidazoles Isoproterenol Male Muscarinic Agonists Myocardium Pertussis Toxin Prazosin Propanolamines Rats Rats, Sprague-Dawley Receptors, Adrenergic, beta-1 Receptors, Adrenergic, beta-2 Second Messenger Systems Virulence Factors, Bordetella

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