Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture

Renata Ciccarelli, Francesc X. Sureda, Giacomo Casabona, Patrizia Di Iorio, Alessandra Caruso, Francesca Spinella, Daniele Filippo Condorelli, Ferdinando Nicoletti, Francesco Caciagli

Research output: Contribution to journalArticle

Abstract

In non-synchronized, subconfluent secondary cultures of rat cortical astrocytes, the selective group-I metabotropic glutamate (mGlu) receptor agonist 3,5-dihydroxyphenylglycine (DHPG) increased [methyl-3H]-thymidine incorporation. This effect was mediated by the activation of the mGlu5 receptor, which was shown to be present by either RT-PCR or Western blot analysis. The mixed mGlu receptor antagonist (+)-α-methyl-4-carboxyphenylglycine reduced the increase in both intracellular Ca9+ and [methyl-3H]thymidine incorporation produced by DHPG. In contrast, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycylopropyl)glycine (DCG-IV), a potent and selective agonist of group-II mGlu receptors, reduced [methyl-3H]-thymidine incorporation in non-synchronized astrocyte cultures. The antiproliferative effect of DCC-IV was prevented by the selective group-II mGlu receptor antagonist (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCGIV). The opposite effect of DHPG and DCC-IV on astrocyte proliferation was confirmed in cultures deprived of serum for 48 hours and then stimulated to proliferate with either epidermal growth factor (EGF) or the metabolically stable ATP analogue adenosine 5'-(βχ-imido)-triphosphate (AMP-PNP). We conclude that activation of mGlu5 receptors enhances proliferation in cultured astrocytes, whereas activation of a receptor with pharmacological characteristics similar to those of mGlu2/3 receptors reduces proliferation.

Original languageEnglish
Pages (from-to)390-398
Number of pages9
JournalGLIA
Volume21
Issue number4
DOIs
Publication statusPublished - Dec 1997

    Fingerprint

Keywords

  • Cultured astrocytes
  • DNA synthesis
  • mGlu3 receptors
  • mGlu5 receptors

ASJC Scopus subject areas

  • Immunology

Cite this

Ciccarelli, R., Sureda, F. X., Casabona, G., Di Iorio, P., Caruso, A., Spinella, F., Condorelli, D. F., Nicoletti, F., & Caciagli, F. (1997). Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture. GLIA, 21(4), 390-398. https://doi.org/10.1002/(SICI)1098-1136(199712)21:4<390::AID-GLIA6>3.0.CO;2-7