Activation of Mitogen‐Activated Protein Kinase in Cultured Rat Hippocampal Neurons by Stimulation of Glutamate Receptors

Masahito Kurino, Kohji Fukunaga, Yukitaka Ushio, Eishichi Miyamoto

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Abstract: Mitogen‐activated protein kinase (MAP kinase) was activated by stimulation of glutamate receptors in cultured rat hippocampal neurons. Ten micromolar glutamate maximally stimulated MAP kinase activity, which peaked during 10 min and decreased to the basal level within 30 min. Experiments using glutamate receptor agonists and antagonists revealed that glutamate stimulated MAP kinase through NMDA and metabotropic glutamate receptors but not through non‐NMDA receptors. Glutamate and its receptor agonists had no apparent effect on MAP kinase activation in cultured cortical astrocytes. Addition of calphostin C, a protein kinase C (PKC) inhibitor, or down‐regulation of PKC activity partly abolished the stimulatory effect by glutamate, but the MAP kinase activation by treatment with ionomycin, a Ca2+ ionophore, remained intact. Lavendustin A, a tyrosine kinase inhibitor, was without effect. In experiments with 32P‐labeled hippocampal neurons, MAP kinase activation by glutamate was associated with phosphorylation of the tyrosine residue located on MAP kinase. However, phosphorylation of Raf‐1, the c‐raf protooncogene product, was not stimulated by treatment with glutamate. Our observations suggest that MAP kinase activation through glutamate receptors in hippocampal neurons is mediated by both the PKC‐dependent and the Ca2+‐dependent pathways and that the activation of Raf‐1 is not involved.

Original languageEnglish
Pages (from-to)1282-1289
Number of pages8
JournalJournal of Neurochemistry
Volume65
Issue number3
DOIs
Publication statusPublished - 1995 Sep
Externally publishedYes

Keywords

  • Ca
  • Glutamate receptors
  • Hippocampal neuron
  • Mitogen‐activated protein kinase
  • Protein kinase C
  • Raf‐1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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