The glyceryl ester of prostaglandin E₂mobilizes calcium and activates signal transduction in RAW264.7 cells

Abstract

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, PGE2-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, PGD2-G, or PGF2␣-G but is observed after addition of PGF 2␣. Moreover, PGE2-G, but not PGE2, 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 ␤. The results indicate that PGE2-G triggers Ca 2؉ 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 PGE2.

COX-2 oxidative metabolism of endocannabinoids augments hippocampal synaptic plasticity

“…These results are consistent with our previous findings where inhibition of ERK blocks PGE 2 -G-induced enhancement of synaptic transmission in cultured hippocampal neurons 2007). Recent evidence shows that PGE 2 -G mobilizes intracellular Ca 2+ via IP 3 and PKC pathways in RAW264.7 macrophage cells (Nirodi et al, 2004). Although we did not detect intracellular Ca 2+ in the presence of PGE 2 -G, the PGE 2 -G-induced increase in LTP is attenuated by an IP 3 inhibitor, indicating the involvement of the IP 3 -mediated mobilization of intracellular Ca 2+ in PGE 2 -G-induced increase in LTP.…”

“…Figure 7 shows that the PGE2-Ginduced increase in LTP was blocked by bath application of PD 98059, SB 239063 and 2-APB, while these inhibitors did not significant affect LTP. These results are consistent with our previous findings where the inhibition of ERK/MAPK or IP 3 blocks the PGE 2 -G-mediated effect on inhibitory synaptic transmission 2007), as well as other observations demonstrating that PGE 2 -G triggers an IP 3 -mediated intracellular Ca 2+ mobilization in RAW264.7 macrophage cells (Nirodi et al, 2004).…”

Misidentification of prostamides as prostaglandins

“…Prostamides are produced in vivo (12) and reduce intraocular pressure (13); indeed, bimatoprost (Lumigan™), one compound in a new class of highly efficacious ocular hypotensive agents, is a close analog of prostaglandin F 2 ␣ (PGF 2 ␣ )-ethanolamide (13). Moreover, the glyceryl ester of PGE 2 can mobilize calcium and activate signaling pathways (14).Given that it is unlikely that prostamides and glycerol equivalents produce their biological actions through existing prostaglandin receptors, and therefore are likely to generate a novel set of signaling pathways, it is essential that studies differentiate between the prostaglandins and the prostamides. However, many recent studies demonstrating prostaglandin production use a radioimmunoassay to detect and quantify the prostaglandin.…”

“…Prostamides are produced in vivo (12) and reduce intraocular pressure (13); indeed, bimatoprost (Lumigan™), one compound in a new class of highly efficacious ocular hypotensive agents, is a close analog of prostaglandin F 2 ␣ (PGF 2 ␣ )-ethanolamide (13). Moreover, the glyceryl ester of PGE 2 can mobilize calcium and activate signaling pathways (14).…”

2-Arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells

“…In addition, as BeWo cells express cyclooxygenase 1 (COX1) and 2 (COX2) (Xu et al 2005), prostaglandins and 2-AG oxygenated metabolites may be involved in 2-AGmediated cell death, as CB antagonists only partially reverse these effects. Prostaglandins can induce cell death in several cell types (Pignatelli et al 2005, Huang et al 2009, Liu et al 2013, and it is known that the COX2 metabolites of 2-AG, the prostaglandin glyceryl esters, possess biological activity (Nirodi et al 2004, Sang et al 2007. Additionally, the COX2 metabolites of AEA, the prostamides, can induce cell death in some cell types (Patsos et al 2010, Kuc et al 2012.…”