Shiba K, Mori H, Ichikawa A, Tonami N
Radioisotope Center, School of Medicine, Kanazawa University, Japan.
Life Sci. 1996;59(13):1039-45. doi: 10.1016/0024-3205(96)00419-5.
We investigated the binding characteristics of 125I-(-)-m-iodovesamicol (125I-(-)-mIV), radioiodinated at the meta position of the 4-phenylpiperidine moiety, in cerebral membranes of the rat brain. The receptor binding affinity of (-)-mIV (Ki = 37 nM) was comparable to that of (-)-vesamicol (Ki = 30 nM). The stereoselectivity of (-)-mIV and (-)-vesamicol for the vesamicol receptor was very high [both (-)-mIV and (-)-vesamicol binding more than 20-fold more active than their (+)isomers], and 125I-(-)-mIV had low affinity for the sigma, dopamine, serotonin, adrenaline and acetylcholine receptors. Furthermore, in a saturation binding study using cerebral membrane preparations, (-)-mIV exhibited a Kd of 18.2 nM with maximum number of binding site Bmax of 660 fmol/mg of protein. These results showed that the characteristics of binding between (-)-mIV and (-)-vesamicol to cholinergic binding sites in the rat brain were similar.
我们研究了在大鼠脑细胞膜中，于4-苯基哌啶部分的间位进行放射性碘化的125I-(-)-间碘韦西卡醇（125I-(-)-mIV）的结合特性。(-)-mIV的受体结合亲和力（Ki = 37 nM）与(-)-韦西卡醇（Ki = 30 nM）相当。(-)-mIV和(-)-韦西卡醇对韦西卡醇受体的立体选择性非常高[(-)-mIV和(-)-韦西卡醇的结合活性均比其(+)-异构体高20倍以上]，且125I-(-)-mIV对σ、多巴胺、5-羟色胺、肾上腺素和乙酰胆碱受体的亲和力较低。此外，在使用脑膜制剂的饱和结合研究中，(-)-mIV的解离常数Kd为18.2 nM，最大结合位点数Bmax为660 fmol/mg蛋白质。这些结果表明，(-)-mIV和(-)-韦西卡醇与大鼠脑中胆碱能结合位点的结合特性相似。
