Evidence of multiple receptor sites within the putative calcium channel.
[3H]-Nimodipine a potent calcium channel blocker, binds to an apparently homogenous population of receptors in guinea-pig brain membranes (KD=0.62 nM, Hill coefficient or approximately 1.0). Diltiazem (10(-5) M) lowers the KD for [3H]-nimodipine by a factor of 3 without changing the maximum number of binding sites. Diltiazem decreased the dissociation rate constant of the nimodipine-receptor complex from 0.18 min-1 to 0.049 min-1 and altered the pharmacological profile as revealed by displacement studies with (-) and (+) verapamil, (-) and (+) prenylamine and 1,4 dihydropyridines. In conclusion [3H]-nimodipine binding can be utilized as a tool to evaluate complex molecular interactions between calcium channel blockers.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D009553:Nimodipine; D011299:Prenylamine / Q000494:pharmacology; D011955:Receptors, Drug / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D009539:Nicotinic Acids; D011955:Receptors, Drug; D009553:Nimodipine; D014700:Verapamil; D004110:Diltiazem; D011299:Prenylamine; D002118:Calcium