Adenosine inhibition of calmodulin-sensitive adenylate cyclase from bovine cerebral cortex.
Calmodulin (CaM)-sensitive adenylate cyclase has recently been purified extensively from bovine brain. In this study, the sensitivity of the CaM-sensitive adenylate cyclase to adenosine and adenosine analogs was examined. The highly purified enzyme preparation retained sensitivity to inhibition by adenosine and adenosine analogs with ribose ring modifications, but not to those with purine ring modifications. Adenosine inhibition of this enzyme was not dependent on GTP and was noncompetitive with respect to ATP. Enzyme that had been dissociated from functional guanine nucleotide binding protein interactions by gel filtration in the presence of the zwitterionic detergent 3-[3-(cholamidopropyl)-dimethylammonio]-propanesulfonate and Mn2+ retained sensitivity to adenosine inhibition. The Ki for adenosine inhibition of the CaM-sensitive adenylate cyclase was approximately 2.6 X 10(-4) M. 5'-Guanylylimidodiphosphate and CaM did not affect the Ki of 3'-deoxyadenosine for the enzyme, but the presence of Ca2+ in the millimolar range raised the Ki by a factor of 5. These results show that the CaM-sensitive form of adenylate cyclase from bovine brain is subject to adenosine inhibition, and strongly suggest that this inhibition is due to interaction of ligands with a purine-specific ("P") site located on the catalytic subunit of the enzyme.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000302:isolation & purification; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D002540:Cerebral Cortex / Q000201:enzymology*; D003839:Deoxyadenosines / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D003839:Deoxyadenosines; D006165:Guanylyl Imidodiphosphate; D000262:Adenylyl Cyclases; D000241:Adenosine; D002118:Calcium