Synergistic activation of bovine cerebellum adenylate cyclase by calmodulin and ?-adrenergic agonists.

The relationship between calmodulin-dependent and ?-adrenergic-sensitive adenylate cyclase activities was examined in membrane preparations from bovine cerebellum. Although stimulation by ?-adrenergic agonists or calmodulin can occur independently, it is shown that their simultaneous presence has a strong synergistic effect on enzyme activity. Calmodulin did not influence the regulatory components of the neurotransmitter-dependent pathway as shown by the lack of effect on (1) receptor affinity, (2) GTP requirement for receptor-mediated activation, (3) rate of activation by guanyl 5?-yl imidodiphosphate [Gpp(NH)p]. Conversely, isoproterenol and guanine nucleotides did not modify to a significant extent the characteristics of enzyme stimulation by Ca(2+) and calmodulin. Furthermore, calmodulin and Gpp(NH)p-dependent activities displayed different sensitivities to thermal inactivation. Our results indicate that ?-adrenergic agonists and calmodulin interact with the same catalytic activity in cerebellar membranes, but presumably via two independent pathways.