期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 7, 页码 1840-1845出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0303950101
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资金
- NCI NIH HHS [R01 CA089450, CA89450, P30 CA068485, CA 68485] Funding Source: Medline
- NIDDK NIH HHS [P30 DK020593, DK 58404, P60 DK020593, P30 DK058404, DK 20593] Funding Source: Medline
- NIGMS NIH HHS [GM15431, P01 GM015431, P50 GM015431] Funding Source: Medline
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 Ca2+ accumulation in a murine macrophage-like cell line, RAW264.7. Ca2+ 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 (IP3) 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, IP3 receptor, and phospholipase C beta. The results indicate that PGE(2)-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 PGE(2)-G to PGE(2).
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