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

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

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 188 KB
• Volume: 21
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199712)21:4<390::aid-glia6>3.0.co;2-7

✦ Synopsis

In non-synchronized, subconfluent secondary cultures of rat cortical astrocytes, the selective group-I metabotropic glutamate (mGlu) receptor agonist 3,5dihydroxyphenylglycine (DHPG) increased [methyl-3 H]-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 (ϩ)-␣-methyl-4carboxyphenylglycine reduced the increase in both intracellular Ca 2ϩ and [methyl-3 H]thymidine incorporation produced by DHPG. In contrast, (2S,1ЈR,2ЈR,3ЈR)-2-(2,3-dicarboxycylopropyl)glycine (DCG-IV), a potent and selective agonist of group-II mGlu receptors, reduced [methyl-3 H]-thymidine incorporation in non-synchronized astrocyte cultures. The antiproliferative effect of DCG-IV was prevented by the selective group-II mGlu receptor antagonist (2S,1ЈS,2ЈS,3ЈR)-2-(2Ј-carboxy-3Ј-phenylcyclopropyl)glycine (PCCG-IV). The opposite effect of DHPG and DCG-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 5Ј-(␤,␥-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.