2-arachidonyl-glycerol stimulates nitric oxide release from human immune and vascular tissues and invertebrate immunocytes by cannabinoid receptor 1

The pharmacological physiological effects of the endogenous cannabinomimeti c (endocannabinoid) anandamide have been well characterized. Another endoca nnabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2- AG occurs in vertebrate and invertebrate tissues and binds to both cannabin oid receptors (CB1 and CB2). In the current study, 2-AG was found to cause human monocytes and immunocytes from Mytilus edulis to become round and imm obile, which may correlate with decreased production of cytokines and adhes ion molecules, i.e. an immunosuppressive response. In addition, exposure of these cells to 2-AG results in nitric oxide (NO) release, which is blocked by the nitric oxide synthase inhibitor, L-NAME and a CB1 antagonist, but n ot by a CB2 antagonist. The results obtained in the human vascular system w ere similar to those obtained in immune cells. Treatment of human saphenous veins and atria with 2-AG stimulated basal NO release, which was antagoniz ed by L-NAME and a CBI antagonist. Taken together these results indicate th at 2-AG exerts immune and vascular actions similar to those observed with a nandamide. (C) 2000 Academic Press.