Activation of protein kinase C by phorbol dibutyrate modulates GABA(A) receptor binding in rat brain slices

Seikwan Oh, Choon Gon Jang, Tangeng Ma, Ing Kang Ho

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Effects of protein kinase C (PKC) activation on the function of the GABA/benzodiazepine receptor-chloride complex were analyzed by quantitative autoradiography using [3H]muscimol, [3H]flunitrazepam and [35S]TBPS in rat brain slices. The density of [3H]muscimol binding was highest in cerebellar granular layers and high in both the frontal cortex and thalamus, but binding levels in the hippocampus were low. After activation of PKC by 100 nM phorbol-12,13-dibutyrate (PDBu), [3H]muscimol binding was decreased in the frontal cortex, striatum and thalamus, but binding levels were not changed in the hippocampus or cerebellum. The density of [3H]flunitrazepam binding was high in the cortex, hippocampus and molecular layers of cerebellum but was low in thalamus. PDBu increased the [3H]flunitrazepam binding only in the striatum and in part of the cortex and thalamus after activation of PKC. After activation of PKC by PDBu, [35S]TBPS binding was increased in most areas, but binding levels were not changed in the brainstem or cerebellum. The receptor binding was markedly decreased in almost all areas by the addition of 2.5 mM Mg2+. Elevated [35S]TBPS binding produced by PDBu was significantly inhibited by the addition of Mg2+. These results suggest that the activation of PKC potentiates benzodiazepine and TBPS binding, but decreases muscimol binding in a region-specific manner in the rat brain. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalBrain Research
Volume850
Issue number1-2
DOIs
StatePublished - 11 Dec 1999

Keywords

  • Autoradiogram
  • Flunitrazepam
  • GABA
  • Muscimol
  • PDBu
  • TBPS

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