Calmodulin stimulates adenylate cyclase activity and increases dopamine activation in bovine retina.
Adenylate cyclase activity in bovine retina is highly responsive to Ca2+ and the endogenous Ca2+-binding protein, calmodulin (CaM). CaM stimulated adenylate cyclase activity in washed particulate fractions of bovine retina by 6.6-fold in a Ca2+-dependent manner. Activation of adenylate cyclase activity by CaM was maximal at 0.12 microM free Ca2+. The apparent Ka for calmodulin stimulation of adenylate cyclase was 67 nM and the apparent Vmax was 116 pmol/min/mg of protein above basal activity. Adenylate cyclase activity in bovine retina was stimulated approximately 50% by guanosine 5'-triphosphate (GTP), but the nonhydrolyzable GTP analogue, guanosine-5'-(beta, gamma-imido)triphosphate (Gpp(NH)p), was able to activate the enzyme nearly 5-fold. CaM and Gpp(NH)p appeared to be partially competitive activators of adenylate cyclase in the retina particulate fraction. Dopamine stimulated adenylate cyclase activity in the presence of GTP with an apparent Ka of 1.0 microM and an apparent Vmax of 66 pmol/min/mg of protein. Ca2+ and CaM increased the apparent Vmax of the dopamine-stimulated adenylate cyclase activity more than 2-fold to a level of 146 pmol/min/mg of protein but did not alter the apparent Ka. This suggests that CaM is an endogenous modulator of dopamine-stimulated adenylate cyclase activity in the retina. CaM-stimulated adenylate cyclase activity may be a common component to retina since we found this activity in retinas from rabbit, rat, and goldfish as well as cow.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D004298:Dopamine / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D012160:Retina / Q000201:enzymology*
D002147:Calmodulin; D006165:Guanylyl Imidodiphosphate; D004533:Egtazic Acid; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D002118:Calcium; D004298:Dopamine