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.