Molecular Pharmacology, Vol 14, 1073-1078, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Metal and Metal-ATP Interactions with Human Platelet Adenylate Cyclase: Effects of Alpha Adrenergic Inhibition

¹ Pharmakologisches Institut der Universität Heidelberg, D-6900 Heidelberg, Federal Republic of Germany

In human platelet lysates, metal and metal-ATP interactions with adenylate cyclase have been studied, using Mg⁺⁺ as divalent cation. The kinetic pattern followed Michaelis-Menten kinetics and conformed to a bireactant mechanism in which free metal served as a requisite activator. The alpha adrenergic component of epinephrine (20 µM) reduced V_max of the enzyme by about 60% without changing the apparent affinities for the substrate, Mg-ATP, and the activator, free Mg⁺⁺. The inhibition was partial and noncompetitive, with an apparent K_I value of 2 µM for epinephrine.

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ACKNOWLEDGMENTS We are grateful to Ms. Gabriele Gabel for superb technical assistance and to Dr. Roger A. Johnson for his helpful advice during the kinetic experiments.