Abstract
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.
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.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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