N-Arachidonylglycine is a potent GPR18 agonist with an EC50 value of 44.5nM [1]. N-Arachidonylglycine acts an endogenous inhibitor of GLYT2 (IC50=3μM) that has the capacity to modulate nociception [2]. N-Arachidonylglycine can increase the intracellular Ca²⁺ level in neurons by activating GPR92[3]. N-Arachidonylglycine has been widely used to promote the production of reactive oxygen species in liver mitochondria and the release of cytochrome c[4].
In vitro, N-Arachidonylglycine treatment (10µM) for 3 days significantly inhibited the secretion of IFNγ and IL-17 in CD4+ T cells[5]. Treatment with 10nM N-Arachidonylglycine for 24 hours significantly promoted the proliferation of BV-2 cells and activation of the MAPK pathway[6].
In vivo, N-Arachidonylglycine treatment via a single intrathecal injection (700nmol; 20µl) for 6h can alleviate mechanical hyperalgesia and thermal hyperalgesia induced by intratibial injection of Freund's complete adjuvant (FCA) in rats[7].
References:
[1] McHugh D, Page J, Dunn E, et al. Δ9‐Tetrahydrocannabinol and N‐arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC‐1B cells[J]. British journal of pharmacology, 2012, 165(8): 2414-2424.
[2] Edington A R, McKinzie A A, Reynolds A J, et al. Extracellular loops 2 and 4 of GLYT2 are required for N-arachidonylglycine inhibition of glycine transport[J]. Journal of Biological Chemistry, 2009, 284(52): 36424-36430.
[3] Yoon J M, Moon M J, Hwang J I, et al. Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92[J]. Journal of Biological Chemistry, 2008, 283(30): 21054-21064.
[4] Zaccagnino P, Saltarella M, D'Oria S, et al. N-arachidonylglycine causes ROS production and cytochrome c release in liver mitochondria[J]. Free Radical Biology and Medicine, 2009, 47(5): 585-592.
[5] Meadows A M, Han K, Singh K, et al. N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+ T cell responsiveness[J]. Iscience, 2023, 26(5).
[6] McHugh D, Hu S S J, Rimmerman N, et al. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor[J]. BMC neuroscience, 2010, 11(1): 44.
[7] Succar R, Mitchell V A, Vaughan C W. Actions of N-arachidonyl-glycine in a rat inflammatory pain model[J]. Molecular pain, 2007, 3: 1744-8069-3-24.
N-Arachidonylglycine是一种强效的GPR18激动剂，EC50值为44.5nM[1]。N-Arachidonylglycine作为一种内源性GLYT2抑制剂（IC50=3μM），具有调节伤害感受的能力[2]。N-Arachidonylglycine可通过激活 GPR92增加神经元内Ca2+水平[3]。N-Arachidonylglycine已被广泛用于促进肝线粒体中活性氧的产生和细胞色素c的释放[4]。
在体外，10μM的N-Arachidonylglycine处理CD4⁺ T细胞3天，显著抑制了IFNγ和IL-17的分泌[5]。10nM的N-Arachidonylglycine处理BV-2细胞24小时，显著促进了细胞增殖和MAPK通路的激活[6]。
在体内，单次鞘内注射700nmol（20µl）N-Arachidonylglycine持续6小时，可减轻胫骨内注射Freund's complete adjuvant (FCA)诱导的大鼠机械性痛觉过敏和热痛觉过敏[7]。