Calcium channel 'agonist' BAY K 8644 inhibits calcium antagonist binding to brain and PC12 cell membranes.
BAY K 8644, a drug that elicits calcium-dependent muscle contraction, inhibits binding of the voltage-dependent calcium channel antagonist [3H]nitrendipine to brain and PC12 pheochromocytoma cell membranes. This effect is due to high-affinity (Ki = 4.5 nM) competitive inhibition at the binding site for dihydropyridine calcium antagonists. Allosteric sites that mediate calcium channel blockade by non-dihydropyridine calcium antagonists are not similarly affected. Our findings indicate that BAY K 8644 is active at central, as well as peripheral, calcium channels and are compatible with a multi-state model of the voltage-dependent calcium channel in which antagonist drugs promote a closed state of the channel, while BAY K 8644 promotes an open state.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D010673:Pheochromocytoma / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007473:Ion Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium