1,4-DIHYDROPYRIDINES MODULATE GTP HYDROLYSIS BY GO IN NEURONAL MEMBRANES

Several lines of evidence suggest that L-type Ca2+ channels (1.4-dihydropyridine receptors) are modulated by GTP-binding proteins. We have further examined this interaction by measuring the effect of 1,4-dihydropyridines on GTPase activity in brain membranes. Dihydropyridine agonists significantly increased GTPase, reflected by an increase in the maximal rate of GTP hydrolysis, without affecting the affinity for GTP or the binding of a non-hydrolysable analogue of GTP. The stimulating effect on GTPase was abolished by antisera raised against G(o)-alpha but not G(i)-alpha. L-type Ca2+ channels may act as endogenous GTPase activating proteins (GAPs) to stimulate GTP hydrolysis by G(o).