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Activation of protein kinase c by phorbol dibutyrate modulates gaba(a) receptor binding in rat brain slices

Academic Article
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Overview

authors

  • Oh, S.
  • Jang, Choon-Gon
  • Ma, T.
  • Ho, I. K.

publication date

  • December 1999

journal

  • Brain Research  Journal

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.

subject areas

  • Animals
  • Autoradiography
  • Bicyclo Compounds, Heterocyclic
  • Brain Chemistry
  • Enzyme Activation
  • Flunitrazepam
  • GABA Agonists
  • GABA Modulators
  • In Vitro Techniques
  • Ligands
  • Muscimol
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • Rats
  • Receptors, GABA-A
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Research

keywords

  • GABA
  • PDBu
  • TBPS
  • autoradiogram
  • flunitrazepam
  • muscimol
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Identity

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/s0006-8993(99)02127-7

PubMed ID

  • 10629760
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Additional Document Info

start page

  • 158

end page

  • 165

volume

  • 850

issue

  • 1-2

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