Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca++ -binding protein.

Abstract

Membranes of rat caudate nucleus contained a dopamine-dependent adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and a Ca2+-binding protein that activated phosphodiesterase (3'':5''-cyclic AMP 5''-nucleotidohydrolase, EC 3.1.4.17). This activator can be released from the membranes by a phosphorylation with a cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). Under the conditions of membrane phosphorylation and activator release, dopamine failed to activate striatal adenylate cyclase. The basal activity of this enzyme was not decreased by the release of the protein activator but the activation by NaF was reduced. Adenylate cyclase was not phosphorylated when the dopamine activation was blocked after the release of the activator, but other membrane proteins were phosphorylated. The endogenous protein stored in striatal membranes may regulate the intracellular concentration of cAMP by an activation of adenylate cyclase while stored in striatal membrane, and by an activation of phosphodiesterase when released into the cytosol after membrane phosphorylation.