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* Department of Medicine, Cardiovascular Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA; and
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
1Correspondence: 956 BRBII/III, University of Pennsylvania Medical Center, 421 Curie Boulevard, Philadelphia, PA 19104, USA. E-mail: liangb{at}mail.med.upenn.edu
Adenosine released during cardiac ischemia exerts a marked protective effect in the heart that is mediated by the A1 and A3 subtypes of adenosine receptors. The signaling pathways activated by these adenosine receptors have now been characterized in a chick embryo ventricular myocyte culture model of cardioprotection against ischemia. Selective A1 and A3 receptor agonists were shown to activate phospholipases C and D, respectively, to achieve their distinct cardioprotective effects. The specificity of the A3 receptor–phospholipase D interaction was also demonstrated in chick embryo atrial myocytes (which do not express endogenous A3 receptors) that had been transfected with a vector encoding the human A3 receptor. Activation of both endogenous A1 and A3 receptors in ventricular myocytes resulted in a protective response greater than that induced by stimulation of either receptor alone. Agonists that activate both adenosine A1 and A3 receptors may thus prove beneficial for the treatment of myocardial ischemia.—Parsons, M., Young, L., Lee, J. E., Jacobson, K. A., Liang, B. T. Distinct cardioprotective effects of adenosine mediated by differential coupling of receptor subtypes to phospholipases C and D.
Key Words: ischemia • ventricular myocyte • PKC activity • cardioprotection
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