Molecular Pharmacology, Vol 16, 749-756, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

The Mechanism of Partial Agonism in the Beta-Receptor Dependent Adenylate Cyclase of Turkey Erythrocytes

¹ Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

The efficacy of nine different -agonists was measured, using three techniques in parallel: (a) the maximal steady state level of adenylate cyclase activity and (b) the first order rate constant describing the process of adenylate cyclase activation to its permanently active state, in the presence of GppNHp, and (c) the first order rate constant describing the process of cyclase deactivation, from its cAMP producing state to its inactive state. The efficacy of the -agonist as measured by the steady-state adenylate cyclase induced activity is directly proportional to the first order rate constant characterizing the activation of the enzyme by the agonist bound receptor. In contrast, the first order rate constant characterizing the deactivation of the adenylate cyclase from its cAMP producing state to its inactive state is independent of the agonist and of the absolute level of steady-state adenylate cyclase specific activity, which differs for each agonist. These results strongly suggest that the efficacy of a -agonist is solely dependent on the rate of adenylate cyclase activation by the agonist bound receptor.

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