Activation of the A(2A) adenosine receptor inhibits nitric oxide production in glial cells

Chaya Brodie, Peter M. Blumberg, Kenneth A. Jacobson

    Research output: Contribution to journalArticlepeer-review

    69 Scopus citations

    Abstract

    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 A(2A) 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 A(2A) receptor agonist was antagonized by the specific A(2A) receptor antagonist CSC. The A(2A) 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 A(2A) receptor inhibits NO production and iNOS expression likely via increased cAMP.

    Original languageEnglish
    Pages (from-to)139-142
    Number of pages4
    JournalFEBS Letters
    Volume429
    Issue number2
    DOIs
    StatePublished - 12 Jun 1998

    Funding

    FundersFunder number
    National Institute of Diabetes and Digestive and Kidney DiseasesZ01DK031117

      Keywords

      • Adenosine agonist
      • Adenosine receptor
      • C6 cell
      • Cytokine
      • Nitric oxide
      • Tumor necrosis factor

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