Donnan G A, Kaczmarczyk S J, Rowe P J, Figdor R, Mendelsohn F A
J Neurol Sci. 1986 Jun;74(1):111-9. doi: 10.1016/0022-510x(86)90195-4.
The effects of the specific dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were studied on the kinetics of [3H]mazindol binding to striatal membranes of C57 black mice. This radioligand was used to label dopamine uptake sites and when administered in vivo, MPTP caused an irreversible, non-competitive inhibition of mazindol binding, consistent with damage to dopaminergic terminals. This effect was abolished by pretreatment with pargyline, a MAOB inhibitor, suggesting that oxidation of MPTP to the pyridinium moiety, MPP+, is a necessary step for toxicity when mazindol binding is used as an end point. In keeping with these findings, pretreatment of mice with mazindol protected against the dopamine-depleting effects of MPTP in vivo. This data suggests that MPTP exerts its toxic effects via MPP+ which is concentrated intraneuronally via the dopamine uptake system. During this process the neurotoxin irreversibly inactivates the dopamine uptake sites.
研究了特定的多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对[3H]吗茚酮与C57黑小鼠纹状体膜结合动力学的影响。该放射性配体用于标记多巴胺摄取位点，体内给予MPTP时，会导致吗茚酮结合的不可逆、非竞争性抑制，这与多巴胺能终末的损伤一致。单胺氧化酶B（MAOB）抑制剂帕吉林预处理可消除这种作用，提示当以吗茚酮结合作为终点时，MPTP氧化为吡啶鎓部分MPP +是产生毒性的必要步骤。与这些发现一致，用吗茚酮预处理小鼠可在体内保护其免受MPTP的多巴胺耗竭作用。该数据表明，MPTP通过MPP +发挥其毒性作用，MPP +通过多巴胺摄取系统在神经元内浓缩。在此过程中，神经毒素不可逆地使多巴胺摄取位点失活。
