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Molecular Pharmacology, Vol 15, 484-491, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Gangliosides on Adenylate Cyclase Activity in Rat Cerebral Cortical Membranes

C. R. PARTINGTON 1 and J. W. DALY 1

1 Laboratory of Bioorganic Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, 20014

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 Vmax of the enzyme was increased with no apparent change in the Km 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 beta-adrenergic agents, an effect similar in magnitude to that observed by addition of GppNHp to the membrane preparations.

Submitted on August 10, 1978
Accepted on November 20, 1978




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