http://www.cnr.it/ontology/cnr/individuo/prodotto/ID196950

Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. (Articolo in rivista) (literal)

Anno

1999-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1046/j.1432-1327.1999.00631.x (literal)

Alternative label

Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G. (1999)
Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages.
in European journal of biochemistry (Print); FEBS, Federation of european biochemical societies, London (Regno Unito)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G. (literal)

Pagina inizio

258 (literal)

Pagina fine

267 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

264 (literal)

Rivista

European journal of biochemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

1 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1. CNR, Ist Chim Mol Interesse Biol, I-80072 Arco Felice, Italy 2. CNR, Ist Cibernetica, I-80072 Arco Felice, Italy 3. CNR, Ist Biotecnol Proteine Enzimol, I-80072 Arco, Italy 4. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA (literal)

Titolo

Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. (literal)

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 mu M) and lipopolysaccharide (LPS, 200 mu g.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 [H-3]2-AG was cleared from the medium of intact 5774 macrophages (t(1/2) = 19-38 min) and esterified to phospholipids, diacylglycerols and triglycerides or hydrolyzed to [H-3]arachidonic acid and glycerol. These catabolic processes were attenuated differentially by various enzyme inhibitors. Rat circulating macrophages were shown to contain enzymatic activities ibr 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 K-m = 110 mu M and V-max = 7.9 nmol.min(-1)(mg protein)(-1) was partially characterized in 5774 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. (literal)

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