Brodie C, Blumberg P M, Jacobson K A
Department of Life Science, Bar-Ilan University, Ramat Gan, Israel.
FEBS Lett. 1998 Jun 12;429(2):139-42. doi: 10.1016/s0014-5793(98)00556-0.
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-gamma and TNF-alpha/IL-1beta and on the production of TNF-alpha. 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-gamma or TNF-alpha/IL-1beta, 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-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 A2A receptor inhibits NO production and iNOS expression likely via increased cAMP.
选择性腺苷受体激动剂和拮抗剂对脑缺血的结局有显著影响，且腺苷受体在星形胶质细胞上表达。在本研究中，我们检测了各种腺苷受体激动剂对脂多糖/γ干扰素（LPS/IFN-γ）和肿瘤坏死因子-α/白细胞介素-1β（TNF-α/IL-1β）激活的星形胶质细胞中一氧化氮（NO）生成、诱导型一氧化氮合酶（iNOS）表达以及TNF-α生成的影响。用A2A受体激动剂CGS 21680处理细胞，可抑制LPS/IFN-γ或TNF-α/IL-1β刺激诱导的NO生成和iNOS表达，而A1和A3受体激动剂，即环戊腺苷（CPA）和氯-异丁基-甲基黄嘌呤（Cl-IB-MECA），则没有显著的抑制作用。A2A受体激动剂的抑制作用被特异性A2A受体拮抗剂CSC拮抗。A2A激动剂对TNF-α的生成也有轻微的抑制作用。环磷酸腺苷（cAMP）升高试剂，如福斯可林和二丁酰环磷腺苷，对NO生成也有类似的抑制作用。我们的研究结果表明，A2A受体的激活可能通过增加cAMP来抑制NO生成和iNOS表达。
