Kilbourn M R, Charalambous A, Frey K A, Sherman P, Higgins D S, Greenamyre J T
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
J Cereb Blood Flow Metab. 1997 Mar;17(3):265-72. doi: 10.1097/00004647-199703000-00003.
The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C]dihydrorotenol ([11C]DHROL: 40%) and in vitro binding of [3H]dihydrorotenone ([3H]DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C]DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C]DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C]iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases.
在单侧纹状体内注射喹啉酸或1-甲基-4-苯基吡啶盐（MPP+）后，检测了放射性标记鱼藤酮类化合物与大鼠纹状体线粒体复合体I的体内和体外结合情况。注射神经毒素13天后，喹啉酸导致注射侧纹状体中[11C]二氢鱼藤醇（[11C]DHROL）的体内结合显著且类似地减少（40%），以及[3H]二氢鱼藤酮（[3H]DHR）的体外结合减少（53%）。MPP+给药后1.5至6小时测量显示，其使[11C]DHROL的体内结合减少高达55%。喹啉酸或MPP+注射后[11C]DHROL体内结合的减少与用[14C]碘安替比林测量的纹状体血流量变化无关。这些结果与放射性标记鱼藤酮类化合物的复合体I结合位点丧失一致，这是由细胞死亡（喹啉酸）或对结合位点的直接竞争（MPP+）产生的。适当放射性标记的鱼藤酮类化合物可能有助于对神经退行性疾病中复合体I变化进行体内成像研究。
