Ca2+-dependent inhibition of smooth muscle adenylate cyclase activity.
We have examined the inhibitory regulation by Ca2+ of the adenylate cyclase activity associated with microsomes isolated from bovine aorta smooth muscle. In the presence of 2 mM MgCl2, Ca2+ (0.8-100 microM) inhibited in a noncompetitive manner activation of the enzyme by GTP, Gpp[NH]p, or forskolin. In all instances the value for half-maximal inhibition was between 2 and 3 microM. In contrast, Ca2+ inhibited the activation by MgCl2 (2-50 mM), alone or in the presence of GTP, in a competitive manner. The inhibition of adenylate cyclase by 10 microM Ca2+ was reversed in the presence of either 5 or 25 microM calmodulin or troponin C. These data show that (i) Ca2+, at concentrations similar to those which activate smooth muscle contraction, inhibits the stimulation of adenylate cyclase by several activators; (ii) Ca2+ and Mg2+ compete for a common site on the smooth muscle adenylate cyclase complex; and (iii) the reversal of Ca2+-dependent inhibition by Ca2+-binding proteins may be produced by chelation of the metal by these proteins.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D002417:Cattle; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D014336:Troponin / Q000502:physiology; D019209:Troponin C
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D004224:Diterpenes; D014336:Troponin; D019209:Troponin C; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D008274:Magnesium; D002118:Calcium