p44/42ERK1/2 MAPK and PLD activation by PGD2 preserves papillary phosphatidylcholine homeostasis

Abstract Previous works from our laboratory demonstrated that PGD 2 modulates phosphatidylcholine (PC) biosynthesis in renal papillary tissue. In the present work, we have evaluated the mechanism by which PGD 2 exerts this action. PGD 2 caused two stimulatory waves in PC synthesis which were reproduced by its full-agonist BW245C. At 1 min stimulation, PGD 2 increased PC synthesis by 131%; this increase was blocked by neomycin and ethanol, cheleritrine and U0126, PLD, PKC, and MEK1/2 inhibitors, respectively. A second PC synthesis increase (100%) was observed after 15 min, which was blocked by PLD inhibitors. PGD 2 also increased phospho-ERK1/2 MAPK in a biphasic-fashion, which was abolished by PLC and PKC inhibitors but not by ethanol, which overincreased phospho-ERK1/2, suggesting that PGD 2 -induced ERK1/2 activation requires previous PLC–PKC activation while PLD down-regulates it. Our results indicate that PGD 2 stimulatory effect involves both PLD and ERK1/2-MAPK activation, and both pathways operate independently of PC synthesis homeostasis.