Interaction of calcium channel blockers with non-neuronal benzodiazepine binding sites.
The ability of calcium channel blockers to displace the binding of benzodiazepine ligands was investigated in rat heart, kidney, and brain. The dihydropyridine calcium channel blockers nifedipine and nitrendipine displaced the binding of the non-neuronal-site ligand [3H]Ro5-4864, but not that of the neuronal-site ligands [3H]flurazepam or [3H]clonazepam. The inhibition was competitive, with Ki values in the micromolar range. Other calcium channel blockers--i.e., verapamil and diltiazem--were inactive at both sites. Thus, non-neuronal benzodiazepines bind to a class of sites that also binds dihydropyridines. This implies a role for benzodiazepines in the mediation of calcium-dependent phenomena.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009568:Nitrendipine; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009568:Nitrendipine; D009543:Nifedipine