The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells.
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 PGE(2), PGE(2)-G, triggers rapid, concentration-dependent Ca(2+) accumulation in a murine macrophage-like cell line, RAW264.7. Ca(2+) mobilization is not observed after addition of PGE(2), PGD(2)-G, or PGF(2alpha)-G but is observed after addition of PGF(2alpha). Moreover, PGE(2)-G, but not PGE(2), stimulates a rapid but transient increase in the levels of inositol 1,4,5-trisphosphate (IP(3)) as well as the membrane association and activation of PKC. PGE(2)-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, IP(3) receptor, and phospholipase C beta. The results indicate that PGE(2)-G triggers Ca(2+) mobilization, IP(3) synthesis, and activation of PKC in RAW264.7 macrophage cells at low concentrations. These responses are independent of the hydrolysis of PGE(2)-G to PGE(2).
Nirodi
Chaitanya S
CS
Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Crews
Brenda C
BC
Kozak
Kevin R
KR
Morrow
Jason D
JD
Marnett
Lawrence J
LJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D015232:Dinoprostone / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D011982:Receptors, Prostaglandin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D002118:Calcium