Relation to the Regulation of Receptor Affinity and Density

more slowly than the desensitization of A1 adenosine receptor-mediated inhibition of adenylate cyclase (t112=11.4O0.7 hours versus 7.5± 1 hours, mean±SEM, n=12 and 6, respectively). Thus, the two A1 adenosine receptor-linked functional responses desensitized differently in response to chronic exposure of the myocyte to R-PIA. Binding of the antagonist radioligand [3H] 8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX) in membranes from myocytes preexposed to R-PIA demonstrated a time-dependent decrease in receptor density without any change in the affinity for the antagonist radioligand. Computer analyses of agonist competition with [3H]CPX binding in membranes from control and R-PIA-treated myocytes revealed a conversion of the high-affinity A1 adenosine receptor to a low-affinity form such that after 24 hours of 1 ,uM R-PIA exposure, all of the receptors were in a low-affinity form. On the other hand, downregulation of the receptor was partial, with nearly 60%o of the receptor remaining after 24-hour treatment with 1 ,uM R-PLIA. These data indicate that the mechanism of desensitization of the A1 adenosine receptor-mediated negative inotropic response differs from that of the desensitization of the adenylate cyclase. Uncoupling of the A1 adenosine receptor from a high-affinity state