M2 muscarinic receptors inhibit cell proliferation in human glioblastoma cell lines

Life Sci. 2012 Nov 27;91(21-22):1134-7. doi: 10.1016/j.lfs.2012.04.033. Epub 2012 Apr 30.

Abstract

Aims: In the present work we investigated the expression of M2 muscarinic receptor subtype in two glioblastoma cell lines and its role in the control of cell proliferation.

Main methods: The M2 receptor transcript and protein expression was studied using RT-PCR and western blot analysis. (3)[H]-thymidine incorporation was used to evaluate cell proliferation in the presence or in the absence of M(2) agonist arecaidine.

Key findings: We demonstrated that M(2) receptor is expressed in both cell lines, although U251 cells show a higher expression level, compared to U87 cells. The activation of M(2) receptors by the agonist arecaidine decreases cell growth in a dose and time dependent manner. The anti-proliferative effect of arecaidine is also confirmed by the significant decrease of (3)[H]-thymidine incorporation in both cell lines. Moreover the M2 antagonist gallamine counteracts the arecaidine effects confirming M2 receptor involvement in glioma cell growth inhibition.

Significance: These data suggest a role for M2 receptors in the inhibition of glioma cell proliferation and the possibility of exploiting these receptors as new promising tools for glioblastoma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arecoline / analogs & derivatives
  • Arecoline / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Receptor, Muscarinic M2 / agonists
  • Receptor, Muscarinic M2 / antagonists & inhibitors
  • Receptor, Muscarinic M2 / genetics
  • Receptor, Muscarinic M2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Receptor, Muscarinic M2
  • arecaidine
  • Arecoline