Evidence for cyclooxygenase activation by nitric oxide in astrocytes

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Abstract
We have evaluated the role of nitric oxide (NO) on the cyclooxygenase pathway in mouse glial cells. Exposure of primary cultures of neonatal mouse cortical astrocytes to bacterial lipopolysaccharide (LPS; 1 μg/ml, 18 h) caused an increase in the release of both nitrite (NO−2) and prostaglandin E2 (PGE22), products of NO synthase (NOS) and cyclooxygenase, respectively. Production of both, NO−2 and PGE2 by astrocytes, was inhibited by the exposure of the NOS inhibitor Nw‐nitro‐L‐arginine methyl ester (L‐NAME: 1, 10, and 100 μM) in a dose related manner. Besides, other NOS inhibitors such as Nitro L‐arginine (NNA: 10−3 M) prevented the increase in PGE2 release from LPS‐stimulated astrocytes. Sodium nitroprusside (SNP; 100–200 μM) used as a NO donor caused a dose‐related enhancement in the accumulation of PGE2 induced by LPS and the presence of hemoglobin blocked the SNP effects. The exposure to SNP counteracted the decrease of PGE2 production in LPS‐treated astrocytes in which NO synthesis was blocked by L‐NAME. In addition, SNP also enhanced the synthesis of PGE2 following exogenous arachidonic acid astrocytes exposure. Interestingly, this effect was blocked by indomethacin. Treatment of astrocytes cultures with dexamethasone (0.1, 1 μM) blocked dose‐relatedly the LPS‐induced release of both NO−2 and PGE2. As expected, the presence of indomethacin (1, 10, and 20 μM) prevented in a dose related fashion, PGE2 production by astrocytes following exposure to LPS. These results strongly indicate that in astroglial cells, NO is able to activate the cyclooxygenase pathway.