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

被引:58
作者
Brodie, C [1 ]
Blumberg, PM
Jacobson, KA
机构
[1] Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel
[2] NCI, MMTP, LCCTP, Bethesda, MD 20892 USA
[3] NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA
来源
FEBS LETTERS | 1998年 / 429卷 / 02期
关键词
C6; cell; nitric oxide; adenosine agonist; adenosine receptor; tumor necrosis factor; cytokine;
D O I
10.1016/S0014-5793(98)00556-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Selective adenosine receptor agonists and antagonists have marked effects on the outcome of cerebral ischemia, and adenosine receptors are expressed on astrocytes. Zn 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-gamma and TNF-alpha/IL-1 beta and on the production of TNF-alpha 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-gamma or TNF-alpha/IL-1 beta, whereas the A(1) and A(3) receptor agonists, CPA and CI-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-alpha. 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. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:139 / 142
页数:4
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