The effects of Ca2+ and calmodulin on adenylyl cyclase activity in plasma membranes derived from neural and non-neural cells.

The regulation of adenylyl cyclase activity by varying concentrations of Ca2+ was examined in plasma membrane preparations derived from a number of neural and non-neural cells. Enzyme activity in neural tissue (i.e. cerebellum) neural-derived pheochromocytoma PC12 cells and certain endocrine cells (i.e. pancreatic RINm5f and parathyroid cells) was stimulated by physiologic concentrations of Ca2+ by a calmodulin (CaM)-dependent mechanism. In contrast, adenylyl cyclase activity in non-neural cells (e.g. platelets and GH3 cells) was not stimulated by Ca2+. In these latter sources, enzyme activity was inhibited by increasing concentrations of Ca2+, independent of CaM. In liver membranes, Ca2+ and/or CaM did not alter adenylyl cyclase activity. These results demonstrate that the effects exerted by physiologic concentrations of Ca2+ on adenylyl cyclase activity range from CaM-dependent stimulation of activity to no effect, to CaM-independent inhibition of activity. The actions of Ca2+ on adenylyl cyclase may be major contributors to the various synergistic or antagonistic interactions that are seen between cAMP-generating and Ca(2+)-mobilizing systems.