Molecular Pharmacology, Vol 19, 256-263, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Calmodulin on Dopamine-Sensitive Adenylate Cyclase Activity in Rat Striatal Membranes

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109

The effect of an endogenous calcium-binding protein, calmodulin, on basal and dopamine-stimulated adenylate cyclase activity in rat striatum was studied. Basal adenylate cyclase activity in a rat striatal particulate preparation depleted of calmodulin was stimulated by calmodulin as well as the guanyl nucleotides, guanosine triphosphate and guanyl-5'-yl-imidodiphosphate. The presence of guanyl nucleotides was required for dopamine stimulation of adenylate cyclase activity in the membrane preparation. Calcium inhibited dopamine-stimulated adenylate cyclase activity, decreasing the maximal velocity by 50%. When calmodulin was added to the assay with calcium, the V_max was restored to that found in the absence of calcium and the K_act for dopamine was further decreased more than 2-fold. The effects of calmodulin on basal and dopamine-sensitive adenylate cyclase activity were specific for calmodulin, since these effects were not obtained in the presence of troponin C, a calcium-binding protein from muscle. This work demonstrates that calmodulin is important both for the sensitivity of striatal adenylate cyclase to dopamine and the maximal velocity of the reaction. Furthermore, this work suggests that, in the presence of physiological concentrations of calcium, dopamine stimulation would be curtailed unless calmodulin were present.

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ACKNOWLEDGMENT We would like to thank Dr. John Dedman, Department of Cell Biology, Baylor College of Medicine, Houston, Tex., for his generous gift of troponin C.