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Molecular Pharmacology, Vol 15, 484-491, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics
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
-adrenergic agents, an effect similar in
magnitude to that observed by addition of GppNHp to the membrane preparations.
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