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Activation of PAF receptors results in enhanced synthesis of 2‐arachidonoylglycerol (2‐AG) in immune cells
Author(s) -
Berdyshev Evgueni V.,
Schmid Patricia C.,
Krebsbach Randy J.,
Schmid Harald H. O.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0181com
Subject(s) - endocannabinoid system , anandamide , 2 arachidonoylglycerol , cannabinoid receptor , microbiology and biotechnology , stimulation , immune system , chemistry , receptor , biology , pharmacology , antagonist , biochemistry , endocrinology , immunology
The endocannabinoid signaling system is believed to play a down‐regulatory role in the control of cell functions. However, little is known about the factors activating endocannabinoid synthesis and which of two known endocannabinoids, 2‐arachidonoylglyc‐erol (2‐AG) or N ‐arachidonoylethanolamine (20:4 n ‐6 NAE, anandamide), is of physiological importance. We approached these questions by studying a possible link between cell activation with 1‐ O ‐alkyl‐2‐acetyl‐ sn ‐glycero‐3‐phosphocholine (platelet‐activating factor, PAF) and the generation of 2‐AG and anandamide in human platelets and mouse P388D1 macrophages. Human platelets responded to stimulation with the production of various 1‐ and 2‐monoacylglycerols, including 2‐AG, whereas stimulation of P388D1 macrophages induced the rapid and selective generation of 2‐AG, which was immediately released into the medium. The effect of PAF was receptor mediated, as PAF receptor antagonist BN52021 blocked the effect. The treatment did not change the content of anandamide in either macro‐phages or platelet‐rich plasma. The inhibitors of PI‐and PC‐specific phospholipases C (U73122 and D609) as well as PI3‐kinase inhibitor (wortmannin) attenuated PAF‐induced 2‐AG production in macrophages. These data suggest a direct role for the endocannabinoid system in controlling immune cell activation status and indicate that 2‐AG rather than anandamide is the endo‐cannabinoid rapidly produced in response to proin‐flammatory stimulation of immune cells.—Berdyshev, E. V., Schmid, P. C., Krebsbach, R. J., Schmid, H. H. O. Activation of PAF receptors results in enhanced synthesis of 2‐arachidonoylglycerol (2‐AG) in immune cells. FASEB J. 15, 2171–2178 (2001)