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The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Biosynthesis and inactivation of the endocannabinoid 2‐arachidonoylglycerol in circulating and tumoral macrophages

Open access
Di Marzo, Vincenzo, Bisogno, Tiziana, De Petrocellis, Luciano, Melck, Dominique, Orlando, Pierangelo, Wagner, Jens A., Kunos, George·1999·European Journal of Biochemistry

Abstract

The stimulus‐induced biosynthesis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) in intact mouse J774 macrophages and the inactivation of 2‐AG by the same cells or by rat circulating macrophages was studied. By using gas chromatography‐mass spectrometry, we found that ionomycin (5 µ m) and lipopolysaccharide (LPS, 200 µg·mL−1) cause a 24‐fold and 2.5‐fold stimulation of 2‐AG levels in J774 cells, respectively, thus providing unprecedented evidence that this cannabimimetic metabolite can be synthesized by macrophages. In J774 cells, LPS also induced a 7.8‐fold increase of the levels of the other endocannabinoid, anandamide, and, in rat circulating macrophages, an almost twofold increase of 2‐AG levels. Extracellular [3 H]2‐AG was cleared from the medium of intact J774 macrophages (t1/2 = 19–28 min) and esterified to phospholipids, diacylglycerols and triglycerides or hydrolyzed to [3 H]arachidonic acid and glycerol. These catabolic processes were attenuated differentially by various enzyme inhibitors. Rat circulating macrophages were shown to contain enzymatic activities for the hydrolysis of 2‐AG, including: (a) fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide breakdown and previously shown to catalyse also 2‐AG hydrolysis, and (b) a 2‐AG hydrolase activity different from FAAH and down‐regulated by LPS. High levels of FAAH mRNA were found in circulating macrophages but not platelets, which, however, contain a 2‐AG hydrolase. Both platelets and macrophages were shown to express the mRNA for the CB1 cannabinoid receptor. A macrophage 2‐AG hydrolase with apparent Km = 110 µ m and Vmax = 7.9 nmol·min−1·(mg protein)−1 was partially characterized in J774 cells and found to exhibit an optimal pH of 6–7 and little or no sensitivity to typical FAAH inhibitors. These findings demonstrate for the first time that macrophages participate in the homeostasis of the hypotensive and immunomodulatory endocannabinoid 2‐AG through metabolic mechanisms that are subject to regulation.

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Crossref · 10.1046/j.1432-1327.1999.00631.x

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Metadata

Authors
Di Marzo, V., Bisogno, T., De Petrocellis, L., Melck, D., Orlando, P., Wagner, J. A., & Kunos, G.
Venue
European Journal of Biochemistry
Publisher
Wiley
Published
1999-08-15
Volume
264
Issue
1
Pages
258-267
ISSN
  • 0014-2956 (ISSN-L)
  • 1432-1033
OpenAlex
W2006730284
Cited by
296
References
42
FWCI
12.72
Type
journal article
Language
en
Open access
bronze

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Di Marzo, V., Bisogno, T., De Petrocellis, L., Melck, D., Orlando, P., Wagner, J. A., & Kunos, G. (1999). Biosynthesis and inactivation of the endocannabinoid 2‐arachidonoylglycerol in circulating and tumoral macrophages. European Journal of Biochemistry. https://doi.org/10.1046/j.1432-1327.1999.00631.x

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