Albus U, Habermann E, Ferry D R, Glossmann H
J Neurochem. 1984 Apr;42(4):1186-9. doi: 10.1111/j.1471-4159.1984.tb12729.x.
The effects of the novel 1,4-dihydropyridine Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate] on the release of [3H]noradrenaline in cultured PC 12 cells were investigated. K+ in a concentration-dependent manner evoked 3H-transmitter release with an EC50 of 50-56 mM. Bay K 8644 at 30 nM potentiated the K+-evoked [3H]noradrenaline release; however, in the absence of calcium neither K+ evoked nor Bay K 8644 enhanced [3H]noradrenaline release. At a K+ concentration of 25 mM, Bay K 8644 stimulated [3H]noradrenaline release fivefold, with an EC50 of 10 nM, and 100 nM of the calcium channel blocker nitrendipine shifted the concentration response curve of Bay K 8644 to the right in an apparently competitive fashion. Nitrendipine blocked the Bay K 8644-potentiated release with an EC50 of 700 nM in the presence of 500 nM Bay K 8644. [3H]Nitrendipine bound to a saturable population of binding sites on PC 12 cell membranes with a Bmax of 180 fmol X mg-1 of membrane protein and a KD of 0.9 nM. Bay K 8644 inhibited [3H]nitrendipine binding with a Ki of 16 nM. It is concluded that Bay K 8644 binds to, and stabilizes, the open state of calcium channels and thus acts as a "calcium agonist" to mediate calcium-dependent cellular events such as catecholamine release from PC 12 cells.
研究了新型1,4 - 二氢吡啶Bay K 8644[甲基 - 1,4 - 二氢 - 2,6 - 二甲基 - 3 - 硝基 - 4 - (2 - 三氟甲基苯基) - 吡啶 - 5 - 羧酸盐]对培养的PC12细胞中[3H]去甲肾上腺素释放的影响。钾离子以浓度依赖的方式诱发3H递质释放，其半数有效浓度（EC50）为50 - 56 mM。30 nM的Bay K 8644增强了钾离子诱发的[3H]去甲肾上腺素释放；然而，在无钙的情况下，钾离子既不能诱发也不能被Bay K 8644增强[3H]去甲肾上腺素释放。在钾离子浓度为25 mM时，Bay K 8644刺激[3H]去甲肾上腺素释放增加了五倍，其EC50为10 nM，100 nM的钙通道阻滞剂尼群地平以明显的竞争性方式使Bay K 8644的浓度 - 反应曲线右移。在存在500 nM Bay K 8644的情况下，尼群地平以700 nM的EC50阻断Bay K 8644增强的释放。[3H]尼群地平与PC12细胞膜上一组可饱和的结合位点结合，其最大结合容量（Bmax）为180 fmol X mg-1膜蛋白，解离常数（KD）为0.9 nM。Bay K 8644以16 nM的抑制常数（Ki）抑制[3H]尼群地平结合。结论是Bay K 8644与钙通道的开放状态结合并使其稳定，因此作为“钙激动剂”介导钙依赖性细胞事件，如PC12细胞中儿茶酚胺的释放。
