Hicks G A, Hudson A L, Henderson G
Department of Pharmacology, University of Bristol, School of Medical Sciences, U.K.
Neuroscience. 1994 Jul;61(2):285-92. doi: 10.1016/0306-4522(94)90231-3.
The rat substantia nigra zona reticulata contains a high density of binding sites for glibenclamide, an adenosine triphosphate-sensitive potassium channel inhibitor, but the precise location of glibenclamide binding sites within this area has not previously been examined. By combining neurochemical lesion and autoradiographical studies we have shown that high affinity [3H]glibenclamide binding sites are located on striatonigral terminals. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle or of quinolinic acid into the striatum were performed in anaesthetized adult rats to lesion the nigrostriatal and striatonigral pathways respectively. Autoradiography was performed on coronal sections of midbrain with [3H]glibenclamide, [3H]YM-09151-2 (dopamine D2 receptor antagonist) and [3H]SCH 23390 (dopamine D1 receptor antagonist) at three rostrocaudal levels of the substantia nigra. Under the conditions of the incubation [3H]glibenclamide binds primarily to the high affinity site. Following the 6-hydroxydopamine nigrostriatal lesion, D2 receptor binding was reduced (by up to 67%) on the lesioned side at all three levels of the substantia nigra whereas D1 receptor and glibenclamide binding were not significantly affected. In contrast, following striatonigral pathway lesion with quinolinic acid D2 receptor binding was unchanged on the lesioned side, but both D1 receptor and glibenclamide binding were reduced at all three levels (by up to 85% and 63% in the area of maximum lesion, respectively). In adjacent sections, the pattern of D1 binding loss was closely paralleled by the loss of glibenclamide binding. These results demonstrate that the high affinity glibenclamide binding sites of the substantia nigra zona reticulata are, at least in part, located on the terminals of striatonigral projection neurons.
大鼠黑质网状部含有高密度的格列本脲结合位点，格列本脲是一种三磷酸腺苷敏感性钾通道抑制剂，但该区域内格列本脲结合位点的确切位置此前尚未被研究过。通过结合神经化学损伤和放射自显影研究，我们发现高亲和力的[3H]格列本脲结合位点位于纹状体黑质终末。在麻醉的成年大鼠中，向内侧前脑束单侧注射6-羟基多巴胺或向纹状体注射喹啉酸，分别损伤黑质纹状体和纹状体黑质通路。在黑质的三个 rostrocaudal 水平上，用[3H]格列本脲、[3H]YM-09151-2（多巴胺 D2 受体拮抗剂）和[3H]SCH 23390（多巴胺 D1 受体拮抗剂）对中脑冠状切片进行放射自显影。在孵育条件下，[3H]格列本脲主要与高亲和力位点结合。在6-羟基多巴胺黑质纹状体损伤后，在黑质的所有三个水平上，损伤侧的 D2 受体结合减少（高达67%），而 D1 受体和格列本脲结合没有受到显著影响。相比之下，在用喹啉酸损伤纹状体黑质通路后，损伤侧的 D2 受体结合没有变化，但在所有三个水平上，D1 受体和格列本脲结合都减少了（在最大损伤区域分别高达85%和63%）。在相邻切片中，D1 结合丧失的模式与格列本脲结合丧失密切平行。这些结果表明，黑质网状部的高亲和力格列本脲结合位点至少部分位于纹状体黑质投射神经元的终末。
