title: Influence of Mg++ on the effect of diltiazem to increase dihydropyridine binding to receptors on Ca++-channels in chick cardiac and skeletal muscle membranes.
abstract: The influence of Mg++ on the effect of diltiazem to increase ligand binding to a high-affinity state of dihydropyridine receptors on voltage-dependent Ca-channels has been studied in chick cardiac and skeletal muscle membranes at 25 degrees C. The high-affinity binding of the Ca-channel inhibitors (+)-[3H]PN 200-110 and [3H]nitrendipine to cardiac membranes was depressed markedly by EDTA and restored fully by the addition of free Mg++ (Ptasienski et al., Biochem. Biophys. Res. Commun. 129: 910-917, 1985). Similar results have now been obtained with skeletal muscle membranes. In the presence of EDTA alone, diltiazem, which binds to another receptor on the Ca-channel, increased the high-affinity binding of both ligands to cardiac and skeletal muscle membranes. However, in the presence of added Mg++, diltiazem had smaller or no effects on the binding of these dihydropyridines. Analyses of the data indicated that both Mg++ and diltiazem could increase the maximum binding (Bmax) for these ligands, but the effect of diltiazem was smaller than, and not additive to, that of Mg++. Specific binding of the Ca-channel activator [3H]Bay k 8644 was only observed in assays containing Mg++ in excess of EDTA. The Bmax for [3H]Bay k 8644 in skeletal muscle membranes was less than that for [3H]PN 200-110 and [3H]nitrendipine, whereas with cardiac membranes equal Bmax values were obtained for all ligands. Diltiazem increased the Bmax for [3H]Bay k 8644 in skeletal muscle, but not in cardiac membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002645:Chickens; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017275:Isradipine; D008274:Magnesium / Q000494:pharmacology*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D004110:Diltiazem; D008274:Magnesium; D002118:Calcium; D017275:Isradipine