[3H]diltiazem binding to calcium channel antagonists recognition sites in rat cerebral cortex.
The presence of a diltiazem recognition site within the macromolecular complex of the calcium channel in the brain had been hypothesized on the basis of binding studies with [3H]dihydropyridine calcium channel antagonists. In the present study, we therefore characterized [3H]diltiazem binding sites in the rat cerebral cortex. Saturable high affinity (Kd = 50-170 nM) [3H]diltiazem binding to the rat cerebral cortex was stereospecifically inhibited by the enantiomers of diltiazem according to their activity as calcium channel antagonists and modulators of [3H]dihydropyridine binding. An association between the [3H]diltiazem binding site and the calcium channel was further corroborated by the effects of chemically heterogeneous calcium channel antagonists on [3H]diltiazem binding. Dihydropyridines appeared to allosterically affect [3H]diltiazem binding according to their pharmacological effects; e.g. at 37 degrees C nitrendipine enhanced whereas the calcium agonist Bay K 8644 failed to affect [3H]diltiazem binding at concentrations fully inhibiting [3H]nitrendipine binding. The effect of nitrendipine may, at least in part, be explained by an increase in the affinity of [3H]diltiazem.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D015220:Calcium Channels; D002540:Cerebral Cortex / Q000378:metabolism*; D004110:Diltiazem / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014316:Tritium
D001552:Benzazepines; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D014316:Tritium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D004110:Diltiazem; D009543:Nifedipine