Gould R J, Murphy K M, Snyder S H
Mol Pharmacol. 1984 Mar;25(2):235-41.
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, KD approximately equal to 0.1-0.2 nM, the value in skeletal muscle is 2 nM. This difference is affinity is also reflected in the Ki 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 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 calcium channel antagonists.
已用[³H]尼群地平标记了大脑皮层、心脏、回肠和骨骼肌中的钙通道拮抗剂结合位点。虽然该位点与皮层、心脏和回肠的解离常数相似，KD约等于0.1 - 0.2 nM，但在骨骼肌中的值为2 nM。这种亲和力差异也反映在二氢吡啶类钙通道拮抗剂硝苯地平、尼莫地平、PY108068、SKF24260和尼索地平以及钙通道激动剂CGP 28392的Ki值上，所有这些对骨骼肌结合位点的亲和力都较低。然而，二苯基烷基胺类钙通道拮抗剂利多氟嗪、桂利嗪、氟桂利嗪和普尼拉明在骨骼肌中的亲和力相对于其他三种组织增加了3至10倍。用EDTA处理膜会降低皮层、心脏和回肠中的结合，但会增加骨骼肌中的结合。加入CaCl₂、SrCl₂或BaCl₂后，这些变化是可逆的。不同组织中[³H]尼群地平结合的不同特性可能与组织对有机钙通道拮抗剂的敏感性不同有关。
