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.
Caldwell
K K
KK
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Boyajian
C L
CL
Cooper
D M
DM
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D004702:Endocrine Glands / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D000262:Adenylyl Cyclases; D002118:Calcium