Ferry D R, Goll A, Gadow C, Glossmann H
Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):183-7. doi: 10.1007/BF00500915.
The optically pure phenylalkylamine Ca2+-antagonist (-)-3H-desmethoxyverapamil has been used to directly label putative Ca2+ channels in thaw-mounted guinea-pig brain sections and in hippocampus homogenates. The autoradiographic distribution of (-)-3H-desmethoxyverapamil binding shows the highest density of binding sites in the molecular layer of the hippocampus, medium levels in the cerebral cortex and low levels in the cerebellum. This anatomical distribution is the same as that found for 1,4-dihydropyridine binding sites, labelled by 3H-nimodipine. (-)-3H-desmethoxyverapamil binds to hippocampus membranes with a KD value of 1.6 +/- 0.2 nmol/l and a Bmax of 870 +/- 175 fmol per mg of protein. Binding is stereospecifically inhibited by the phenylalkylamines desmethoxyverapamil, D-600 and verapamil. 1,4-Dihydropyridines regulate (-)-3H-desmethoxyverapamil binding in a negative heterotropic allosteric manner, depending on the availability of free divalent cations. The potency series of phenylalkylamine Ca2+ antagonists in inhibiting high affinity (-)-3H-desmethoxyverapamil binding to hippocampus membranes and the allosteric regulation by chemically different classes of Ca2+ antagonists suggest that the (-)-3H-desmethoxyverapamil binding sites in hippocampus are associated with putative Ca2+ channels.
光学纯的苯基烷基胺类钙离子拮抗剂（-）-3H-去甲氧基维拉帕米已被用于直接标记解冻后的豚鼠脑切片和海马匀浆中的假定钙离子通道。（-）-3H-去甲氧基维拉帕米结合的放射自显影分布显示，海马分子层中结合位点密度最高，大脑皮层中结合位点密度中等，小脑结合位点密度低。这种解剖学分布与用3H-尼莫地平标记的1,4-二氢吡啶结合位点的分布相同。（-）-3H-去甲氧基维拉帕米与海马膜结合的KD值为1.6±0.2 nmol/l，Bmax为每毫克蛋白质870±175 fmol。去甲氧基维拉帕米、D-600和维拉帕米等苯基烷基胺类物质对结合具有立体特异性抑制作用。1,4-二氢吡啶类物质以负性异向变构方式调节（-）-3H-去甲氧基维拉帕米的结合，这取决于游离二价阳离子的可用性。苯基烷基胺类钙离子拮抗剂抑制高亲和力（-）-3H-去甲氧基维拉帕米与海马膜结合的效价顺序以及不同化学类别的钙离子拮抗剂的变构调节表明，海马中的（-）-3H-去甲氧基维拉帕米结合位点与假定的钙离子通道相关。
