The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells

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FONTE

National Academy of Sciences

RESUMO

Glyceryl prostaglandins (PG-Gs) are generated by the oxygenation of the endocannabinoid, 2-arachidonylglycerol, by cyclooxygenase 2. The biological consequences of this selective oxygenation are uncertain because the cellular activities of PG-Gs have yet to be defined. We report that the glyceryl ester of PGE2, PGE2-G, triggers rapid, concentration-dependent Ca2+ accumulation in a murine macrophage-like cell line, RAW264.7. Ca2+ mobilization is not observed after addition of PGE2, PGD2-G, or PGF2α-G but is observed after addition of PGF2α. Moreover, PGE2-G, but not PGE2, stimulates a rapid but transient increase in the levels of inositol 1,4,5-trisphosphate (IP3) as well as the membrane association and activation of PKC. PGE2-G induces a concentration-dependent increase in the levels of phosphorylated extracellular signal regulated kinases 1 and 2 through a pathway that requires the activities of PKC, IP3 receptor, and phospholipase C β. The results indicate that PGE2-G triggers Ca2+ mobilization, IP3 synthesis, and activation of PKC in RAW264.7 macrophage cells at low concentrations. These responses are independent of the hydrolysis of PGE2-G to PGE2.

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