Acetylcholine as a mitogen: Muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells

Marina Guizzetti, Paola Costa, Janet Peters, Lucio G. Costa

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

The mitogenic effect of muscarinic receptor agonists in glial cells has been characterized in rat cortical astrocytes and human 132 1N1 astrocytoma cells. The muscarinic receptor agonist carbachol caused a dose- and time-dependent increase in proliferation, as measured by [3H]thymidine incorporation. The mitogenic effect was mimicked by several muscarinic, but not nicotinic receptor agonists, and was blocked by muscarinic receptor antagonists. Reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated the presence of m2, m3 and to a lesser degree, m5 muscarinic receptor mRNA in both astrocytes and astrocytoma cells. Proliferation experiments with subtype-specific muscarinic receptor antagonists suggest that carbachol-induced proliferation is due to activation of muscarinic M3 receptors. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) also stimulated glial cell proliferation. Down-regulation of protein kinase C, or the protein kinase C antagonist 1,5-(isoquinolynsulfanyl)-2-methylpiperazine dihydrochloride (H7) blocked proliferation induced by either TPA or carbachol. Of other neurotransmitters tested, histamine caused glial cell proliferation, norepinephrine and γ-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalEuropean Journal of Pharmacology
Volume297
Issue number3
DOIs
StatePublished - Feb 22 1996

Keywords

  • Astrocyte
  • Astrocytoma
  • Cell proliferation
  • Muscarinic receptor

ASJC Scopus subject areas

  • Pharmacology

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