A novel mechanism for the inhibition of adenylate cyclase via inhibitory GTP-binding proteins. Calmodulin-dependent inhibition of the cyclase catalyst by the beta gamma-subunits of GTP-binding proteins.
The adenylate cyclase catalytic protein partially purified from rat brain membranes was activated by the stimulatory GTP-binding protein (Gs), forskolin, and Ca2+-calmodulin. The Ca2+-calmodulin-stimulated activity was markedly, but the Gs- or forskolin-stimulated activity was essentially not, inhibited by low concentrations of the beta gamma-subunits of the inhibitory GTP-binding protein (Gi). The inhibition appeared to be competitive with calmodulin. On the other hand, the association of increasing amounts of beta gamma with the alpha of Gi, which was measured based on the ADP-ribosylation by islet-activating protein, pertussis toxin, was apparently competed by Ca2+-calmodulin. Furthermore, beta gamma bound to calmodulin-Sepharose in the presence of Ca2+, but not in its absence. Thus, the direct interaction of beta gamma with calmodulin is a likely mechanism involved in beta gamma-induced inhibition of the calmodulin-stimulated adenylate cyclase.
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D046911:Macromolecular Substances; D037342:Pertussis Toxin; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D046911:Macromolecular Substances; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins