Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [(3)H]GABA release

FEBS Lett. 2000 Mar 10;469(2-3):159-62. doi: 10.1016/s0014-5793(00)01272-2.

Abstract

Kainate receptors are ionotropic receptors, also reported to couple to G(i)/G(o) proteins, increasing neuronal excitability through disinhibition of neuronal circuits. We directly tested in hippocampal synaptosomes if kainate receptor-mediated inhibition of GABA release involved a metabotropic action. The kainate analogue, domoate (3 microM), inhibited by 24% [(3)H]GABA-evoked release, an effect reduced by 76% in synaptosomes pre-treated with pertussis toxin. Protein kinase C inhibition attenuated by 82% domoate-induced inhibition of GABA release whereas protein kinase C activation did not change kainate receptor binding. Thus, domoate inhibition of GABA release recruits G(i)/G(o) proteins and a protein kinase C pathway.

MeSH terms

  • Animals
  • GTP-Binding Proteins / metabolism
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • In Vitro Techniques
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Male
  • Pertussis Toxin*
  • Presynaptic Terminals / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Kainic Acid / metabolism
  • Receptors, Kainic Acid / physiology*
  • Receptors, Presynaptic / metabolism
  • Synaptosomes / metabolism
  • Virulence Factors, Bordetella / pharmacology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Receptors, Kainic Acid
  • Receptors, Presynaptic
  • Virulence Factors, Bordetella
  • gamma-Aminobutyric Acid
  • Pertussis Toxin
  • Protein Kinase C
  • GTP-Binding Proteins
  • domoic acid
  • Kainic Acid