Calcium channel antagonist binding sites have been labeled in cerebral cortex, heart, ileum, and skeletal muscle with [3H]nitrendipine. While the dissociation constants of the site from cortex, heart, and ileum are similar, K(D) ≃ 0.1-0.2 nM, the value in skeletal muscle is 2 nM. This difference in affinity is also reflected in the K(i) values of dihydropyridine calcium channel antagonists, nifedipine, nimodipine, PY108068, SKF24260, and nisoldipine, and the calcium channel agonist CGP 28392, all of which show lower affinity for the skeletal muscle binding site. The diphenylalkylamine calcium channel antagonists, lidoflazine, cinnarizine, flunarizine, and prenylamine, however, show a 3- to 10-fold increase in affinity in skeletal muscle relative to the other three tissues. EDTA treatment of membranes decreases binding in cortex, heart, and ileum but increase 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 calcium channel antagonists.
|Number of pages||7|
|State||Published - 1984|