Reduction of Proportion of Process‐Bearing Phenotype of Microglial Cell Line <scp>MG6</scp> by Arachidonic Acid Generated From Exogenous Lysophosphatidylinositol

Attention has recently been paid to the cross-talk between G protein-coupled receptor 55 for lysophosphatidylinositol as an endogenous agonist and cannabinoid receptors 1 and 2 for 2-arachidonoylglycerol as an endogenous agonists in mammalian neuronal cells. In relation to the functional coupling, in this study, exogenously added 1-arachidonoyl lysophosphatidylinositol (1-20:4 LPI) to MG6, a mouse microglial cell line, was found to be converted to 1-arachidonoyl glycerol (1-20:4 MAG) and arachidonic acid (20:4 FFA), possibly due to the combined action of ecto-lysophospholipaase C activity of glycerophosphodiesterase 3 and extracellular lipase toward MAG. Consistent with the above result, exogenous 1-20:4 MAG was found to be converted to 20:4 FFA by extracellular lipase activity toward MAG in the culture medium of MG6 cells. Not only was exogenous 20:4 FFA incubated with MG6 cells, but also 20:4 FFA produced from the exogenous 1-20:4 MAG and 1-20:4 LPI in the absence of fetal bovine serum, respectively, were postulated to be involved in the reduced population of process-bearing MG6 cells via its entry into the cells and the intracellular conversion of prostaglandins. This hypothesis was supported by our findings showing that the reducing effects of exogenous 1-20:4 LPI, 1-20:4 MAG, and 20:4 FFA were all found to be indomethacin-inhibitable, and that exogenous PGD₂, but not PGE₂ and PGF₂α, was shown to reduce the population of process-bearing MG6 cells cultured without Fetal bovine serum.