EVIDENCE FOR NEGATIVE COOPERATIVITY AMONG BETA-ADRENERGIC RECEPTORS IN CARDIAC AND LUNG-TISSUE OF GUINEA-PIG

Stereospecific binding sites for (-)-[3H]dihydroalprenolol, a β-adrenergic antagonist, have been identified in guinea-pig myocardial cell membranes and lung tissue preparations. A close correlation between the abilities of β-adrenergic antagonists to compete with labelled antagonist binding and to block the response of isoproterenol plus Gpp(NH)p† stimulated adenylate cyclase has been found. Equilibrium binding of (-)-[3H]dihydroalprenolol to binding sites of cardiac and lung tissue displays characteristics consistent with negative cooperativity among the DHA binding sites: Scatchard plots are curvilinear with upward concavity. The existence of site-site interactions of the negatively cooperative type was demonstrated directly by the ability of unlabelled (-)alprenolol to accelerate the dissociation of (-)-|3H|dihydroalprenolol under conditions where rebinding of the radioligand does not occur. © 1979.