Ca²⁺-dependent regulation of rat caudate nucleus adenylate cyclase and effects on the response to dopamine

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.