Molecular Pharmacology, Vol 20, 319-325, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Ca²⁺-Dependent Regulation of Rat Caudate Nucleus Adenylate Cyclase and Effects on the Response to Dopamine

¹ Department of Pharmacology and Cell Biophysics and Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio 45267

The Ca²⁺ dependence of rat caudate nucleus microsomal adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1] was determined and compared with that of cortical microsomes. Both cyclase preparations exhibited a biphasic response to Ca²⁺ with no differences in the free Ca²⁺ concentrations required to stimulate (one-half maximum = 0.19 µM cortex; 0.2 µM caudate) and inhibit (one-half maximum = 1 µM cortex; 0.9 µM caudate) each cyclase system. Whereas the cortical activity was stimulated 7-fold by Ca²⁺, the caudate activity exhibited only a 2-fold Ca²⁺-induced enhancement of basal cyclase. This relative insensitivity of caudate adenylate cyclase is not due to the selective loss of calmodulin. Ca²⁺ concentrations (0.03-0.5 µM) which stimulate the cyclase and the addition of large excesses of calmodulin had no effect on the ED₅₀ of dopamine. The abilities of Ca²⁺ and dopamine to stimulate caudate adenylate cyclase activity were additive over the concentration range of 0.03-0.5 µM Ca²⁺·Ca²⁺ concentrations (>0.5 µM) which inhibit adenylate cyclase activity abolished the stimulatory effect of dopamine. Therefore, it is suggested that Ca²⁺ and dopamine, in a coordinated manner, can modulate the response of caudate adenylate cyclase.

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ACKNOWLEDGMENTS The authors wish to acknowledge the technical assistance of Henry Zot and the helpful supervision of manuscript preparation by Diane Reed, Deborah Turner, and Joyce Zerkle.