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Preconditioning is a powerful form of (myocardial) protection that follows brief sublethal ischemia. G-protein-coupled receptors constitute the trigger for entrance to the preconditioned state. In conjunction with other receptors, various membrane adenosine receptors play an important role in the transduction of extracellular signals, leading to protection by preconditioning, lasting 1–3 hr. Adenosine A₁- and A₃-receptors mediate inhibition of adenylate cyclase via a guanine nucleotide binding inhibitory protein (G_i/o). A₂-receptors couple to a comparable stimulatory protein (G_s). Adenosine receptors are especially abundant in the central nervous system; in lesser numbers, they are found in many tissues, including the heart. A₁-receptors are located on cardiomyocytes and vascular smooth muscle cells, A₂-receptors on endothelial and vascular smooth muscle cells, and A₃-receptors on ventricular myocytes. Ischemic …