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 Go alpha but not Gi alpha. L-type Ca2+ channels may act as endogenous GTPase activating proteins (GAPs) to stimulate GTP hydrolysis by Go.
Sweeney
M I
MI
Department of Pharmacology, Royal Free Hospital School of Medicine, London, UK.
Dolphin
A C
AC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007106:Immune Sera; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D004095:Dihydropyridines; D007106:Immune Sera; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D001418:Baclofen