ALPHA-ADRENERGIC ANTAGONISTS AS POSSIBLE CALCIUM-CHANNEL INHIBITORS
ALPHA-ADRENERGIC ANTAGONISTS AS POSSIBLE CALCIUM-CHANNEL INHIBITORS
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DOI：
10.1073/pnas.78.2.1237
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
ADLER, M
中科院分区：
文献类型：
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作者：
ATLAS, D;ADLER, M
研究了各种有机Ca 2+通道抑制剂对α 1-拮抗剂3 H-标记的2-[（2“，6”-二甲氧基苯氧基乙基）氨基甲基]-1，4-苯并二氧六环（[3 H]WB-4101）与来自大鼠脑和神经母细胞瘤-神经胶质瘤杂交细胞（NG 108 -15）的膜的结合的影响。通过监测[3 H]WB-4101的结合发现，钙通道抑制剂甲氧维拉帕米（D 600）、维拉帕米和硝苯地平类似物YC-93 [2，6-二甲基-4-甲基-1，2，2，2，2，3-三唑-1-基]-L-吲哚-2-酮（2，6-dimethyl-4-methyl-4-methyl-1，2，2，3，4-dichloro-2-dichloro-2-benzoic acid）可抑制钙通道。（3-硝基苯基）-1，4-二氢吡啶-3，5-二甲酸[（N-苄基-N-甲基氨基）]乙基，5-甲基酯··HCl]结合到大鼠脑中的2个不同位点：一个高亲和力位点（Kd = 2.9 nM和结合能力B = 360 fmol/mg蛋白）和一个低亲和力位点（Kd = 260 nM和B = 2700 fmol/mg蛋白）。在NG 108 -15细胞中，其中用[3 H]WB-4101未检测到α 1受体，Ca 2+拮抗剂以B = 976 fmol/mg蛋白质的能力结合到膜中的非肾上腺素能位点。[~ 3 H]WB-4101位点与Ca ~（2+）拮抗剂的结合导致通过电生理技术研究WB-4101作为Ca ~（2+）抑制剂。WB-4101抑制幅度并降低Ca 2+尖峰的上升速率，其亲和力略大于D 600所观察到的亲和力。对于WB-4101和D 600，Ca 2+尖峰幅度的50%抑制浓度分别为48 μ M和80 μ M。WB-4101诱导的Ca 2+峰的阻断被高Ca 2+浓度拮抗，表明Ca 2+和α-Ca 2+的共同位点。拮抗剂D 600和WB-4101也抑制电压依赖性Na+和K+电导。在脑和NG 108 -15细胞膜制备物中，Ca 2+通道可占[3 H]WB-4101标记位点的一部分。
The effects of various organic Ca2+ channel inhibitors were investigated on the binding of the .alpha.1-antagonist 3H-labeled 2-[(2'',6''-dimethoxyphenoxyethyl)aminomethyl]-1,4-benzodioxane ([3H]WB-4101) to membranes from rat brain and neuroblastoma-glioma hybrid cells (NG108-15). As found by monitoring binding of [3H]WB-4101, the Ca2+ channel inhibitors methoxyverapamil (D600), verapamil and the nifedipine analog YC-93 [2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino)]ethyl, 5-methyl ester.cntdot.HCl] bind to 2 different sites in rat brain: a high-affinity site (Kd = 2.9 nM and binding capacity B = 360 f[femto]mol/mg of protein) and a low-affinity site (Kd = 260 nM and B = 2700 fmol/mg of protein). In NG108-15 cells, where no .alpha.1 receptors were detected with [3H]WB-4101, the Ca2+ antagonists bind to nonadrenergic sites in the membrane with a capacity B = 976 fmol/mg of protein. The binding of Ca2+ antagonists to [3H]WB-4101 sites led to the investigation of WB-4101 as a Ca2+ inhibitor by electrophysiological techniques. WB-4101 depressed the amplitude and reduced the rate of rise of the Ca2+ spike with an affinity slightly greater than that observed for D600. The concentration for 50% inhibition of the Ca2+ spike amplitude was 48 .mu.M for WB-4101 and 80 .mu.M for D600. The WB-4101-induced blockade of the Ca2+ spike was antagonized by high Ca2+ concentrations, indicating a common site for Ca2+ and the .alpha.-antagonist. D600 and WB-4101 also inhibited voltage-dependent Na+ and K+ conductances. Ca2+ channels can account for a fraction of the sites labeled with [3H]WB-4101 in membrane preparations from brain and NG108-15 cells.