Activation of A1 adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100β protein from cultured astrocytes
✍ Scribed by R. Ciccarelli; P. Di Iorio; V. Bruno; G. Battaglia; I. D'Alimonte; M. D'Onofrio; F. Nicoletti; F. Caciagli
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 138 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Pharmacological activation of A 1 adenosine receptor with 2-chloro-N6cyclopentyladenosine (CCPA) or mGlu3 metabotropic glutamate receptors with (2S,2ЈR,3ЈR)-2-(2Ј,3Ј-dicarboxycyclopropyl)glycine (DCG-IV) or aminopyrrolidine-2R,4Rdicarboxylate (2R,4R-APDC) enhanced the release of nerve growth factor (NGF) or S-100 protein from rat cultured astrocytes. Stimulation of release by CCPA and DCG-IV or 2R,4R-APDC was inhibited by the A 1 adenosine receptor antagonist 8-cyclopentyl-1,3dipropylxanthine and by the mGlu2/3 receptor antagonist (2S,1ЈS,2ЈS,3ЈR)-2-(2Ј-carboxy-3Ј-phenylcyclopropyl)glycine (PCCG-4), respectively. Time-course studies revealed a profound difference between the release of S-100 protein and the release of NGF in response to extracellular signals. Stimulation of S-100 protein exhibited rapid kinetics, peaking after 1 h of drug treatment, whereas the enhancement of NGF release was much slower, requiring at least 6 h of A 1 adenosine or mGlu3 receptor activation. In addition, stimulation of NGF but not S-100 release was substantially reduced in cultures treated with the protein synthesis inhibitor cycloheximide. In addition, a 6-8 h treatment of cultured astrocytes with A 1 or mGlu3 receptor agonists increased the levels of both NGF mRNA and NGF-like immunoreactive proteins, including NGF prohormone. We conclude that activation of A 1 adenosine or mGlu3 receptors produces pleiotropic effects in astrocytes, stimulating the synthesis and/or the release of protein factors. Astrocytes may therefore become targets for drugs that stimulate the local production of neurotrophic factors in the CNS, and this may provide the basis for a novel therapeutic strategy in chronic neurodegenerative disorders.