title: Subcellular localization of [3H]-nitrendipine binding sites in guinea-pig ileal smooth muscle.
abstract: The binding of [3H]-nitrendipine was studied in microsomal fractions isolated from guinea-pig ileal smooth muscle. Only one class of specific binding sites was detected, with a KD of 0.4 nM. For various dihydropyridine derivatives, including the stereoisomers of nimodipine and the 'Ca agonist' Bay K 8644, the potency for inhibition of [3H]-nitrendipine binding correlated well with the reported pharmacological potency in smooth muscle preparations. To establish the subcellular localization of [3H]-nitrendipine binding sites, untreated and digitonin-treated microsomal fractions were subfractionated by isopycnic density gradient centrifugation. The density distribution of [3H]-nitrendipine binding was markedly shifted by digitonin towards higher densities, as were the distributions of 5'-nucleotidase and [3H]-ouabain binding, whereas the distributions of NADPH:cytochrome c reductase and NADH:cytochrome c reductase were hardly modified by digitonin. It is concluded that most, if not all, [3H]-nitrendipine binding sites in guinea-pig ileal smooth muscle are present in the plasma membrane, in agreement with the postulated mode of action of dihydropyridines as inhibitors of plasmalemmal Ca channels.
authors.forename: T
authors.initials: T
authors.lastname: Godfraind
authors.forename: M
authors.initials: M
authors.lastname: Wibo
mesh_terms: D015720:5'-Nucleotidase; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000648:ultrastructure; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009130:Muscle, Smooth / Q000648:ultrastructure*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D009708:Nucleotidases / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism
chemical_list: D010042:Ouabain; D009568:Nitrendipine; D009708:Nucleotidases; D015720:5'-Nucleotidase; D009543:Nifedipine; D004072:Digitonin