Pharmacological activation of A1 adenosine receptor with 2-chloro-N6-cyclopentyladenosine (CCPA) or mGlu3 metabotropic glutamate receptors with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) or aminopyrrolidine-2R,4R-dicarboxylate (2R,4R-APDC) enhanced the release of nerve growth factor (NGF) or S-100β protein from rat cultured astrocytes. Stimulation of release by CCPA and DCG-IV or 2R,4R-APDC was inhibited by the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and by the mGlu2/3 receptor antagonist (2S, 1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4), respectively. Time-course studies revealed a profound difference between the release of S-100β protein and the release of NGF in response to extracellular signals. Stimulation of S-100β protein exhibited rapid kinetics, peaking after I h of drug treatment, whereas the enhancement of NGF release was much slower, requiring at least 6 h of A1 adenosine or mGlu3 receptor activation. In addition, stimulation of NGF but not S-100β release was substantially reduced in cultures treated with the protein synthesis inhibitor cycloheximide. In addition, a 6-8 h treatment of cultured astrocytes with A1 or mGlu3 receptor agonists increased the levels of both NGF mRNA and NGF-like immunoreactive proteins, including NGF prohormone. We conclude that activation of A1 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.
|Number of pages||7|
|Publication status||Published - Sep 1999|
- A adenosine receptors
- Cultured astrocytes
- Metabotropic glutamate receptors
- S-100β protein release
ASJC Scopus subject areas