Localization of high affinity [3H]Glibenclamide binding sites within the substantia nigra zona reticulata of the rat brain

GA Hicks, Alan L Hudson, Graeme Henderson

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    27 Citations (Scopus)

    Abstract

    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.

    Translated title of the contributionLocalization of high affinity [3H]Glibenclamide binding sites within the substantia nigra zona reticulata of the rat brain
    Original languageEnglish
    Pages (from-to)285-292
    Number of pages7
    JournalNeuroscience
    Volume61
    Issue number2
    DOIs
    Publication statusPublished - Jul 1994

    Keywords

    • ATP, adenosine triphosphate; ATP-K+, adenosine triphosphate-sensitive potassium channel; 6-OHDA, 6-hydroxydopamine hydrochloride; mfb, medial forebrain bundle; PBS, phosphate-buffered saline; SCH 23390, 7-chloro-8-hydroxy-3-methel-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride; SN, substantia nigra; Tris, 2-amino-2-(hydroxymethyl)-1,3-propanediol; VTA, ventral tegmental area; YM-09151-2, N-[(2RS,3RS)-1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methyl-aminobenzamide

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