Lysophosphatidylcholine inhibits NMDA-induced currents by a mechanism independent of phospholipase A2-mediated protein kinase C activation in hippocampal glial cells.

Lysophosphatidylcholine (LysoPC), which is formed by phospholipase A2 (PLA2)-mediated phosphatidylcholine hydrolysis, is involved in enhancement of the diacylglycerol- or phorbol ester-dependent protein kinase C (PKC) activation. In the present study, the effect of lysoPC on NMDA-evoked currents was examined by whole-cell patches in cultured rat hippocampal glial cells. NMDA activated the receptor channel and produced currents in glial cells. LysoPC reversibly inhibited the NMDA-gated currents by 43% and this inhibition was not affected by a selective PKC inhibitor, GF109203X. These results indicate that lysoPC inhibits NMDA-induced currents by a mechanism independent of PLA2-mediated PKC activation. A possible explanation for the effect could be that lysoPC directly alters channel-gating kinetics of NMDA receptor or interacts with membrane components surrounding NMDA receptors.