ACTIVE UPTAKE OF MPP+, A METABOLITE OF MPTP, BY BRAIN SYNAPTOSOMES

ACTIVE UPTAKE OF MPP+, A METABOLITE OF MPTP, BY BRAIN SYNAPTOSOMES
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DOI:
10.1016/0006-291x(85)91071-x
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发表时间:
1985-01-01
影响因子:
3.1
通讯作者:
CASTAGNOLI, N
CASTAGNOLI, N
中科院分区:
生物学4区
文献类型:
--
作者:
CHIBA, K;TREVOR, AJ;CASTAGNOLI, N

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小鼠脑突触体制剂用于研究 N-甲基-4-苯基吡啶 (MPP+) 的摄取,N-甲基-4-苯基吡啶 (MPP+) 是神经毒素 MPTP(1-甲基-4-苯基-1,2,3,6-四氢吡啶)的代谢产物。纹状体突触体对[3H]-MPP+的摄取为.apprx。比[ 3 H]-MPTP大25倍,KM为0.48μM,Vmax为5.3nmol/g组织/分钟。摄取是Na+依赖性的并且被哇巴因、[可卡因]和多巴胺抑制(Ki 0.12.mu.M)。从纹状体制备的突触体积累[3H]-MPP+的速度比从其他脑区域制备的突触体高5-10倍。 MPP+ 的这种选择性摄取可能有助于 MPTP 对黑质纹状体多巴胺能神经元的毒性作用的特异性。
Mouse brain synaptosomal preparations were used to study uptake of N-methyl-4-phenylpyridine (MPP+), a metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The uptake of [3H]-MPP+ by striatal synaptosomes was .apprx. 25 times greater than that of [3H]-MPTP, with a KM of 0.48 .mu.M and a Vmax of 5.3 nmol/g tissue per min. Uptake was Na+ dependent and inhibited by ouabain, [cocaine] and dopamine (Ki 0.12 .mu.M). Synaptosomes prepared from the corpus striatum accumulated [3H]-MPP+ at a rate of 5-10 times higher than preparations from other brain regions. This selective uptake of MPP+ may contribute to the specificity of the toxic effects of MPTP on nigrostriatal dopaminergic neurons.