Activation of the A2A adenosine receptor inhibits nitric oxide production in glial cells

FEBS Letters - Tập 429 - Trang 139-142 - 1998
Chaya Brodie1, Peter M Blumberg2, Kenneth A Jacobson3
1Department of Life Science, Bar-Ilan University, Ramat Gan 52900, Israel
2MMTP, LCCTP, National Cancer Institute, Bethesda, MD 20892, USA
3Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA

Tóm tắt

Selective adenosine receptor agonists and antagonists have marked effects on the outcome of cerebral ischemia, and adenosine receptors are expressed on astrocytes. In this study we examined the effects of various adenosine receptor agonists on the production of nitric oxide and the induction of iNOS in astrocytes activated by LPS/IFN‐γ and TNF‐α/IL‐1β and on the production of TNF‐α. Treatment of the cells with the A2A receptor agonist CGS 21680 inhibited both NO production and iNOS expression induced by stimulation with either LPS/IFN‐γ or TNF‐α/IL‐1β, whereas the A1 and A3 receptor agonists, CPA and Cl‐IB‐MECA, respectively, did not have significant inhibitory effects. The inhibitory effect of the A2A receptor agonist was antagonized by the specific A2A receptor antagonist CSC. The A2A agonist also exerted a small inhibitory effect on the production of TNF‐α. Similar inhibitory effects on the production of NO were obtained by cyclic AMP‐elevating reagents, such as forskolin and dibutyryl cyclic AMP. Our findings suggest that activation of the A2A receptor inhibits NO production and iNOS expression likely via increased cAMP.

Tài liệu tham khảo

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FEBS Letters

Tập 429

139-142

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