Calcium-dependent regulation of brain adenylate cyclase.
The adenylate cyclase activity of a particulate preparation of rat cerebral cortex is comprised of two contributing components, only one of which requires a CDR for activity. The CDR-dependent component was inhibited by high ratios of Mg2+ to Ca2+, responded in a biphasic manner (activation then inhibition) to increasing free Ca2+ concentrations, was inhibited by 0.1 to 0.4 mM chlorpromazine, and was activated by 1 to 100 micrometer cocaine. This enzyme form, which represented approximately 80% of tge basal activity of a cortex homogenate, was stable during pretreatment of homogenates at 45 degrees C but was completely deactivated by the removal of CDR during the preparation of the particulate fraction. Adenylate cyclase activity that did not depend on CDR was unaffected by the removal of CDR during the preparation of the particulate fraction, had elevated activity at high ratios of Mg2+ to Ca2+, was inhibited by Ca2+, was unaffected by 0.1 to 0.4 mM chlorpromazine and was slightly inhibited by 1 to 100 micrometer cocaine, and was not stable during pretreatment of homogenates at 45 degrees. The CDR-dependent component of adenylate cyclase activity was activated by 5 mM NaF to varying degrees depending on the concentration of CDR present in the assay. NaF decreased the concentration of CDR required to produce half-maximal velocity obtained at optimal concentrations of CDR. Activation by NaF required the presence of Ca2+ and was immediately and completely reversed by EGTA. In contrast, the component that did not respond to CDR was activated four- to fivefold by NaF. This activation was not influenced by Ca2+ or CDR and was not reversed by EGTA. The observed effects of effects of divalent cations on the CDR-dependent enzyme are discussed in relation to the cation-binding properties of CDR. The relationship of the CDR-dependent form of adenylate cyclase to other forms of this enzyme remains to be determined.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000502:physiology*; D002746:Chlorpromazine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology
D004533:Egtazic Acid; D012969:Sodium Fluoride; D000262:Adenylyl Cyclases; D008274:Magnesium; D003042:Cocaine; D002118:Calcium; D002746:Chlorpromazine