Waksman G, Hamel E, Delay-Goyet P, Roques B P
EMBO J. 1986 Dec 1;5(12):3163-6. doi: 10.1002/j.1460-2075.1986.tb04624.x.
The cellular localization of rat brain enkephalinase was studied after induction of selective unilateral lesions using in vitro quantitative autoradiography of the specific binding of the enzyme inhibitor [3H]-N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]glycine ([3H]HACBO-Gly). Twenty-one days following injection of kainic acid in the caudate-putamen (CP) [3H]HACBO-Gly binding was locally decreased by 52% with a concomitant reduction of 67 and 78% in the ipsilateral substantia nigra (SN) and globus pallidus (GP), respectively. Inhibition of axonal transport in the CP by unilateral stereotaxic injection of colchicine induced a large (30-60%) and progressive decrease in enkephalinase labelling within the ipsilateral GP and SN. Taken together these results strongly suggest that in the CP a large fraction of enkephalinase is localized on intrinsic striatal neurones, and that the enzyme present both in the GP and the SN is partly localized on nerve terminals originating from neurones in the CP. No change in [3H]HACBO-Gly binding was observed in the CP following injection of 6-hydroxydopamine in the nigrostriatal bundle, contrasting with the 30% depletion in opioid receptors. This would indicate that enkephalinase is present in only very low amounts, if at all, on striatal dopaminergic nerve terminals.
采用酶抑制剂[3H]-N-[(2RS)-3-羟基氨基甲酰基-2-苄基-1-氧代丙基]甘氨酸([3H]HACBO-Gly)特异性结合的体外定量放射自显影技术，在诱导选择性单侧损伤后，研究大鼠脑内脑啡肽酶的细胞定位。在尾状核-壳核(CP)注射 kainic 酸 21 天后，[3H]HACBO-Gly 结合在局部降低了 52%，同时同侧黑质(SN)和苍白球(GP)分别降低了 67%和 78%。通过单侧立体定向注射秋水仙碱抑制 CP 中的轴突运输，导致同侧 GP 和 SN 内脑啡肽酶标记物大幅(30 - 60%)且逐渐减少。综合这些结果强烈表明，在 CP 中，大部分脑啡肽酶定位于纹状体内源性神经元，并且 GP 和 SN 中存在的该酶部分定位于源自 CP 中神经元的神经末梢。在黑质纹状体束注射 6-羟基多巴胺后，CP 中未观察到[3H]HACBO-Gly 结合的变化，这与阿片受体 30%的耗竭形成对比。这表明纹状体多巴胺能神经末梢上即使存在脑啡肽酶，其含量也极低。
