Marangos P J, Sperelakis N, Patel J
J Neurochem. 1984 May;42(5):1338-42. doi: 10.1111/j.1471-4159.1984.tb02792.x.
The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, and the latter a KD of 0.30 +/- 0.02 nM and a Bmax of 160 +/- 12 fmol/mg protein. The binding site in both brain and heart was highly specific for dihydropyridine calcium antagonists, such as nifedipine, nimodipine, and nisoldipine, since these drugs were several orders of magnitude more potent as inhibitors of [3H]NDP binding than verapamil, methoxyverapamil, or diltiazem. The developmental appearance of [3H]NDP binding sites in brain was rather gradual, with adult levels being attained just prior to birth. This was in contrast to the profile in heart ventricle which showed essentially adult levels at seven days gestation. The acquisition of [3H]NDP binding sites in chick brain roughly paralleled the onset of neuronal maturation and functional activity. In both chick brain and heart, verapamil and methoxyverapamil were weak inhibitors of [3H]NDP binding. However, the inhibition of binding in both tissues was markedly biphasic, with only 50% of the binding sites being susceptible to inhibition by each agent, suggesting that multiple calcium antagonist binding sites may exist in both tissues.
利用[3H]尼群地平（[3H]NDP）作为配体，测定了鸡脑和心室钙拮抗剂结合位点的个体发生情况。[3H]NDP与成年心脏和脑的结合在动力学上非常相似，前者的解离常数（KD）为0.28±0.02 nM，最大结合容量（Bmax）为138±17 fmol/mg蛋白，后者的KD为0.30±0.02 nM，Bmax为160±12 fmol/mg蛋白。脑和心脏中的结合位点对二氢吡啶类钙拮抗剂（如硝苯地平、尼莫地平和尼索地平）具有高度特异性，因为这些药物作为[3H]NDP结合抑制剂的效力比维拉帕米、甲氧维拉帕米或地尔硫䓬强几个数量级。脑内[3H]NDP结合位点的发育出现较为渐进，在出生前才达到成年水平。这与心室的情况形成对比，心室在妊娠七天时就已基本达到成年水平。鸡脑中[3H]NDP结合位点的获得大致与神经元成熟和功能活动的开始同步。在鸡脑和心脏中，维拉帕米和甲氧维拉帕米都是[3H]NDP结合的弱抑制剂。然而，两种组织中结合的抑制作用均明显呈双相性，每种药物仅能抑制50%的结合位点，这表明两种组织中可能存在多个钙拮抗剂结合位点。
