Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells

Irene Cappuccio, Paola Spinsanti, Antonio Porcellini, Francesca Desiderati, Teresa De Vita, Marianna Storto, Loredana Capobianco, Giuseppe Battaglia, Ferdinando Nicoletti, Daniela Melchiorri

Research output: Contribution to journalArticle

Abstract

Cultured mouse embryonic stem (ES) cells maintained under undifferentiated conditions (i.e. grown in medium containing 15% FCS and leukemia inhibitory factor - LIF) expressed mGlu5 metabotropic glutamate receptors. Activation of these receptors with quisqualate increased [Ca2+]i but only when cultures were deprived of extracellular glutamate, indicating that the receptor was saturated by the endogenous glutamate. Pharmacological blockade of mGlu5 receptors with 2-methyl-6-(phenylethynyl)pyridine (MPEP) or antisense-induced knock-down of mGlu5 receptors decreased the expression of the two main transcription factors that sustain ES cell self-renewal, i.e. Oct-4 and Nanog, as assessed by real-time PCR and immunoblotting. Exposure of ES cell cultures to MPEP also reduced alkaline phosphatase activity, a marker of undifferentiated ES cells. These data support a critical role for mGlu receptors in early development showing that mGlu5 receptors are expressed by ES cells and their activation sustains ES cell self-renewal in culture.

Original languageEnglish
Pages (from-to)196-205
Number of pages10
JournalNeuropharmacology
Volume49
Issue numberSUPPL.
DOIs
Publication statusPublished - 2005

Keywords

  • Embryonic stem cells
  • mGlu receptors
  • Nanog
  • Oct-4
  • Self-renewal

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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