Abstract

The addition of 50 µM mixed brain gangliosides to membrane preparations from rat cerebral cortex caused a 50-95% increase in the basal adenylate cyclase activity. The activation was rapid at all temperatures and was relatively irreversible, as evidenced by the fact that repeated washing of the membrane after exposure to gangliosides failed to restore adenylate cyclase activity to its basal level. The V_max of the enzyme was increased with no apparent change in the K_m for the substrate, ATP. The expression of activation of adenylate cyclase by gangliosides showed a marked temperature dependence, with maximal effects seem in the 30-40° range and no activation seen at either 10° or 50°. The activation of adenylate cyclase by brain gangliosides was additive with respect to activation by NaF and detergents, but was not additive with respect to activation by GppNHp or lysolecithin. The activation of the enzyme by gangliosides was unaffected by the presence of calcium ions, calcium-dependent activator protein, or EGTA. The addition of brain gangliosides to the membranes caused a consistent restoration of the responsiveness of the adenylate cyclase system to activation by β-adrenergic agents, an effect similar in magnitude to that observed by addition of GppNHp to the membrane preparations.