Synergistic activation of brain adenylate cyclase by calmodulin, and either GTP or catecholamines including dopamine

Abstract

The effects of calmodulin (CaM), guanosine triphosphate (GTP) and dopaminergic or beta-adrenergic agonists on the activities of adenylate cyclase were studied in EGTA-washed lysed synaptosomal membranes from rat striatum and cerebral cortex. Based on the free calcium ion concentration-dependence of the enzymic activity, it was found that the stimulatory effect of CaM and GTP on adenylate cyclase was synergistic with maximum activation at pCa 6.2 for both striatal and cortical membranes. This was not due to the effect of CaM-dependent phosphodiesterase because exogenous CaM did not affect particulate phosphodiesterase activity. Added CaM not only enhanced the adenylate cyclase activity but acted cooperatively with dopaminergic or beta-adrenergic agonists in the presence of GTP. Most marked was enhancement found for the striatal SKF 38393- (a specific D1 agonist) and the cortical isoproterenol-dependent activities. A synergism was also found for CaM and forskolin. These findings strongly suggest that CaM is involved in the striatal dopaminergic as well as in the cortical beta-adrenergic systems.