Insulin potentiates N-methyl-d-aspartate receptor activity in Xenopus oocytes and rat hippocampus

Lifei Liu, James C. Brown, Wallace W. Webster, Richard A. Morrisett, Daniel T. Monaghan

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

Growth factor signal transduction pathways have recently been shown to affect voltage-gated ion channel activity. In this study we report that insulin can modulate the activity of a ligand-gated ion channel, the N-methyl-d-aspartate (NMDA) receptor. In Xenopus oocytes, brief insulin exposure rapidly potentiated NR1a/NR2A and NR1a/NR2B receptor responses 2-3 fold and weakly potentiated NR1a/NR2C and NR1a/NR2D mediated-responses. Insulin potentiation of NR1a/NR2A receptor responses was significantly blocked by staurosporine, suggesting kinase involvement in insulin action. Insulin modulation of native NMDA receptors is suggested by the observation that insulin potentiated the NMDA receptor-mediated synaptic component in hippocampal slices. Regulation of NMDA receptor activity by growth factors may account for previous observations of growth factor modulation of central nervous system excitotoxicity.

Original languageEnglish (US)
Pages (from-to)5-8
Number of pages4
JournalNeuroscience Letters
Volume192
Issue number1
DOIs
StatePublished - Jun 2 1995

Keywords

  • Growth factors
  • Hippocampus
  • IGF-1
  • Insulin
  • N-methyl-d-aspartate
  • Oocytes
  • PKC
  • Phorbol ester
  • Synaptic transmission

ASJC Scopus subject areas

  • General Neuroscience

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