21-aminosteroids interact with the dopamine transporter to protect against 1-methyl-4-phenylpyridinium-induced neurotoxicity.
21-aminosteroids interact with the dopamine transporter to protect against 1-methyl-4-phenylpyridinium-induced neurotoxicity.
复制标题
21-氨基类固醇与多巴胺转运蛋白相互作用，以防止 1-甲基-4-苯基吡啶鎓诱导的神经毒性。
DOI：
10.1111/j.1471-4159.1992.tb09314.x
复制
发表时间：
1992
影响因子：
4.7
通讯作者：
Weiner,WJ
中科院分区：
文献类型：
--
作者：
Sanchez-Ramos,JR;Song,S;Mash,DC;Weiner,WJ
U-78518 F是一种来自脂质过氧化抑制剂（lazaroids）新家族的21-氨基类固醇，可增加与神经毒素1-甲基-4-苯基吡啶（MPP+）孵育的中脑细胞培养物中多巴胺（DA）神经元的存活率。随着U-78518 F浓度增加至30 μM，发生了对DA神经元死亡的保护作用。非特异性毒性产生较高浓度的MPP+不受lazaroid。U-78518 F抑制[3 H]MPP+和[3 H]DA的细胞摄取，但不抑制γ-[3 H]氨基丁酸。在人纹状体膜制备物中，U-78518 F与[3 H]马吲哚竞争结合DA转运蛋白，计算的Ki值为10 μM。四个lazaroids测试抑制[3 H]DA摄取的细胞培养系统中的两个。21氨基类固醇在MPP+诱导的神经毒性中的保护作用部分是这些药物与DA转运蛋白相互作用的函数。
U‐78518F, a 21‐aminosteroid from the novel family of lipid peroxidation inhibitors (lazaroids), increased survival of dopamine (DA) neurons in mesencephalic cell cultures incubated with the neurotoxinl‐methyl‐4‐phenylpyridinium (MPP+). Protection against DA neuron death occurred with increasing concentrations of U‐78518F up to 30 μM. Nonspecific toxicity produced with higher concentrations of MPP+was not affected by the lazaroid. U‐78518F inhibited cellular uptake of [3H]MPP+and [3H]DA, but not that of γ‐[3H]aminobutyric acid. In human striatal membrane preparations, U‐78518F competed with [3H]mazindol for binding to the DA transporter, with a calculatedKivalue of 10 μM. Two of four lazaroids tested inhibited [3H]DA uptake in the cell culture system. The protective effects of 21‐aminosteroids in MPP+‐induced neurotoxicity are, in part, a function of the interaction of these agents with the DA transporter.