TISSUE HETEROGENEITY OF CALCIUM-CHANNEL ANTAGONIST BINDING-SITES LABELED BY [NITRENDIPINE-H-3

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (2) , 235-241
Abstract
Ca channel antagonist binding sites have been labeled in [guinea pig] cerebral cortex, heart, ileum and skeletal muscle with [3H]nitrendipine. While the dissociation constants of the site from cortex, heart and ileum are similar, KD .simeq. 0.1-0.2 nM, the value in skeletal muscle is 2 nM. This difference in affinity is also reflected in the Ki values of dihydropyridine Ca channel antagonists, nifedipine, nimodipine, PY 108-068 [1,4-dihydro-2,6-dimethyl-4-(benzoxadiazolyl)-3,5-pyridinedicarboxylic acid diethyl ester] SKF24260 [1,4-dihydro-2,6-dimethyl-4-(2-trifluoromethylphenyl)-3,5-pyridinedicarboxylic acid diethyl ester] and nisoldipine, and the Ca channel agonist CGP 28392 [4-(2-(difluoromethoxy)phenyl)-1,4,5,7-tetrahydro-2-methyl-5-oxofuro(3,4-.beta.)pyridine-3-carboxylic acid ethylester] all of which show lower affinity for the skeletal muscle binding site. The diphenylalkylamine Ca channel antagonists, lidoflazine, cinnarizine, flunarizine and prenylamine, show a 3- to 10-fold increase in affinity in skeletal muscle relative to the other 3 tissues. EDTA treatment of membranes decreases binding in cortex, heart and ileum but increases binding in skeletal muscle. These changes are reversible upon addition of CaCl2, SrCl2, or BaCl2. The different properties of [3H]nitrendipine binding in various tissues may relate to the varying tissue sensitivity to organic Ca channel antagonists.