Adenosine receptors in the human heart : pharmacological characterization in nondiseased and cardiomyopathic tissue

The purpose of the present study was to characterize adenosine receptors in human atrial and ventricular preparations as well as in nonfailing and failing human ventricular myocardium. Using the antagonist radioligand 3H-DPCPX, A1-adenosine receptors were identified in human atrial and ventricular myocardial membranes. The rank order of potency of agonists and antagonists as well as the influence of Gpp(NH)p on agonist high affinity binding were similar in atrial and ventricular myocardium, indicating that the same receptor type probably couples in a similar guanine nucleotide-dependent way to different effectors producing the “direct” or “indirect” effects on myocardial force on contraction. The density and coupling of ventricular adenosine receptors as well as the antiadrenergic, “indirect” effect following their stimulation were not different in failing human myocardium, despite an increase in Giα-proteins. Thus, enhanced antiadrenergic effects of A1-adenosine receptors do not contribute to the reduction of cAMP-dependent positive inotropic effects in heart failure. © 1993 Wiley-Liss, Inc.