NMDA-dependent prostaglandin E2 release by human cultured astroglial cells is driven by nitric oxide

The role of the L-arginine-NO pathway on the formation of PGE₂ by human cultured astroglial cells incubated with NMDA has been investigated. Preincubation of T 67 astroglial cell line with NMDA (10-600 μM) produced a significant dose-dependent increase of both nitrite (the breakdown product of NO), PGE₂ and cGMP levels in cell supernatant. This effect was inhibited by coincubation of cells with L-NAME (20-300 μM), an inhibitor of NO synthase showing that the release of PGE₂ subsequent to NMDA receptor stimulation was driven by NO. The release of PGE₂ but not elevation of nitrite and cGMP levels was affected by indomethacin (10 μM), an inhibitor of cyclooxygenase. The inhibitory effect of L-NAME on PGE₂ release by NMDA-pretreated astroglial cells was reverted by arachidonic acid, showing that the effect of NO on PGE₂ release occurred at the cyclo-oxygenase level. Thus, the present experiments demonstrate that the release of PGE₂ by astroglial cells pretreated with NMDA is driven by activation of the L-arginine-NO pathway, and this may be relevant in the pathophysiological mechanisms where glutamatergic neurotransmission is involved.