Resolution of inflammation by N‐arachidonoylglycine

Abstract

N-arachidonoylglycine (NAgly) is an endogenous signaling lipid that is a member of the eicosanoid super family and is related to anandamide. It shows anti-inflammatory activity in vivo in the mouse peritonitis model where it reduces migration of inflammatory leukocytes following injection of pro-inflammatory agents into the peritoneal cavity. Using cell culture models, including GPR18 transfected HEK-293 cells, evidence is presented that the orphan receptor GPR18 is involved in this action. Increases in free arachidonic acid, and robust stimulation of anti-inflammatory eicosanoids were observed at low micro molar concentrations. These included 15-deoxy-delta-13, 14-PGJ2 and lipoxin A4 both of which are believed to mediate the resolution stage of inflammation. It was further shown that NAgly might act via GPR18 activation in promoting the number of Trypan Blue stained cells, a possible indicator of programmed cell death. Thus, we hypothesize that NAgly induces the death of inflammatory cells, a process that is considered to be important for the resolution of inflammation.

Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine

“…Furthermore, it was recently reported that N-arachidonoyl-glycine also possessed anti-inflammatory actions [51]. Meanwhile, N-palmitoyl-glycine seemed to show a proinflammatory effect, suggesting the structural importance of N-acyl-LPC activity.…”

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation

“…Again, CBD was more active than THC in stimulating phopholipid hydrolysis. By way of comparison, the anti inflammatory actions of cannabinoid analogs such as NAgly 24 and ajulemic acid ( Fig. 2) 25 have been attributed to their ability to promote the release of free arachidonic acid.…”

The Atypical Cannabinoid O-1602: Targets, Actions, and the Central Nervous System

“…Using a screening process, these researchers discovered that N-arachidonylglycine (NAGly) stimulated Ca(2+) influx and inihibited forskolin-induced cAMP accumulation in GPR18-transfected cells to a greater extent that control cells, and concluded that NAGly is a endogenous ligand for GPR18. Of particular interest for the central nervous system, there is some evidence that GPR18 may have antinociceptive effects through direct effects on nociceptive fibres [29], though more evidence points towards the modulation of inflammation [30] and pain via effects on immune cells including macrophages [31] and microglia [21] and on vasodilatation.…”