2-Arachidonoyl Glycerol

2-Arachidonoyl glycerol is an endogenous agonist of the cannabinoid (CB) receptors CB1 and CB2 (K_i = 25.3 ~ 472 and 145 ~ 1400 nM, respectively) [1-3].

CB1 receptors are expressed mainly by neurons of the central and peripheral nervous system whilst CB2 receptors occur in certain non-neuronal tissues, particularly in immune cells, with both coupled to G proteins. CB receptors play important roles in the control of memory, cognition, movement and pain perception [1, 3].

In NG108-15 neuroblastoma × glioma hybrid cells, 2-arachidonoyl glycerol, at a concentration of 0.3 nM, induced a rapid, transient increase in intracellular free calcium through a CB1 receptor-dependent mechanism. 2-Arachidonoyl glycerol was the most potent compound examined, when compared with other potent CB receptor agonists including HU-210 and CP55940 [2].

In male Sprague-Dawley rats, 2-arachidonoyl glycerol (0.1 ~ 1.0 mg/kg, i.v.) preferentially stimulated nucleus accumbens (NAc) shell as compared to the NAc core. NAc shell dopamine increased by ~ 25% over basal value at the highest doses tested (0.5 and 1.0 mg/kg, i.v.) [4].

References:

[1]. Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature, 1997, 388(6644): 773-778.

[2]. Sugiura T, Kodaka T, Nakane S, et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. Journal of Biological Chemistry, 1999, 274(5): 2794-2801.

[3]. Pertwee R G. Pharmacology of cannabinoid receptor ligands. Current Medicinal Chemistry, 1999, 6(8): 635-664.

[4]. De Luca M A, Valentini V, Bimpisidis Z, et al. Endocannabinoid 2-arachidonoylglycerol self-administration by Sprague-Dawley rats and stimulation of in vivo dopamine transmission in the nucleus accumbens shell. Front Psychiatry, 2014, 5(140): 1-9.