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Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides.
J Biol Chem. 2002 Nov 22; 277(47):44877-85.JB

Abstract

Cyclooxygenase-2 (COX-2) action on the endocannabinoids, 2-arachidonylglycerol (2-AG) and anandamide (AEA), generates prostaglandin glycerol esters (PG-G) and ethanolamides (PG-EA), respectively. The diversity of PG-Gs and PG-EAs that can be formed enzymatically following COX-2 oxygenation of endocannabinoids was examined in cellular and subcellular systems. In cellular systems, glycerol esters and ethanolamides of PGE(2), PGD(2), and PGF(2alpha) were major products of the endocannabinoid-derived COX-2 products, PGH(2)-G and PGH(2)-EA. The sequential action of purified COX-2 and thromboxane synthase on AEA and 2-AG provided thromboxane A(2) ethanolamide and glycerol ester, respectively. Similarly, bovine prostacyclin synthase catalyzed the isomerization of the intermediate endoperoxides, PGH(2)-G and PGH(2)-EA, to the corresponding prostacyclin derivatives. Quantification of the efficiency of prostaglandin and thromboxane synthase-directed endoperoxide isomerization demonstrated that PGE, PGD, and PGI synthases catalyze the isomerization of PGH(2)-G at rates approaching those observed with PGH(2). In contrast, thromboxane synthase was far more efficient at catalyzing PGH(2) isomerization than at catalyzing the isomerization of PGH(2)-G. These results define the in vitro diversity of endocannabinoid-derived prostanoids and will permit focused investigations into their production and potential biological actions in vivo.

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Authors+Show Affiliations

Kozak KR
Department of Biochemistry, Vanderbilt-Ingram Cancer Center, and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Crews BC
No affiliation info available
Morrow JD
No affiliation info available
Wang LH
No affiliation info available
Ma YH
No affiliation info available
Weinander R
No affiliation info available
Jakobsson PJ
No affiliation info available
Marnett LJ
No affiliation info available

MeSH

AnimalsAortaArachidonic AcidsCannabinoid Receptor ModulatorsCannabinoidsCattleCell LineCyclooxygenase 2EndocannabinoidsEpoprostenolEstersGlyceridesGlycerolHumansIntramolecular OxidoreductasesIsoenzymesLipocalinsMembrane ProteinsMiceMolecular StructureNeurotransmitter AgentsPolyunsaturated AlkamidesProstaglandin-Endoperoxide SynthasesProstaglandinsStereoisomerismThromboxane-A SynthaseThromboxanes

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12244105

Citation

Kozak, Kevin R., et al. "Metabolism of the Endocannabinoids, 2-arachidonylglycerol and Anandamide, Into Prostaglandin, Thromboxane, and Prostacyclin Glycerol Esters and Ethanolamides." The Journal of Biological Chemistry, vol. 277, no. 47, 2002, pp. 44877-85.
Kozak KR, Crews BC, Morrow JD, et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem. 2002;277(47):44877-85.
Kozak, K. R., Crews, B. C., Morrow, J. D., Wang, L. H., Ma, Y. H., Weinander, R., Jakobsson, P. J., & Marnett, L. J. (2002). Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. The Journal of Biological Chemistry, 277(47), 44877-85.
Kozak KR, et al. Metabolism of the Endocannabinoids, 2-arachidonylglycerol and Anandamide, Into Prostaglandin, Thromboxane, and Prostacyclin Glycerol Esters and Ethanolamides. J Biol Chem. 2002 Nov 22;277(47):44877-85. PubMed PMID: 12244105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. AU - Kozak,Kevin R, AU - Crews,Brenda C, AU - Morrow,Jason D, AU - Wang,Lee-Ho, AU - Ma,Y Henry, AU - Weinander,Rolf, AU - Jakobsson,Per-Johan, AU - Marnett,Lawrence J, Y1 - 2002/09/19/ PY - 2002/9/24/pubmed PY - 2003/1/8/medline PY - 2002/9/24/entrez SP - 44877 EP - 85 JF - The Journal of biological chemistry JO - J Biol Chem VL - 277 IS - 47 N2 - Cyclooxygenase-2 (COX-2) action on the endocannabinoids, 2-arachidonylglycerol (2-AG) and anandamide (AEA), generates prostaglandin glycerol esters (PG-G) and ethanolamides (PG-EA), respectively. The diversity of PG-Gs and PG-EAs that can be formed enzymatically following COX-2 oxygenation of endocannabinoids was examined in cellular and subcellular systems. In cellular systems, glycerol esters and ethanolamides of PGE(2), PGD(2), and PGF(2alpha) were major products of the endocannabinoid-derived COX-2 products, PGH(2)-G and PGH(2)-EA. The sequential action of purified COX-2 and thromboxane synthase on AEA and 2-AG provided thromboxane A(2) ethanolamide and glycerol ester, respectively. Similarly, bovine prostacyclin synthase catalyzed the isomerization of the intermediate endoperoxides, PGH(2)-G and PGH(2)-EA, to the corresponding prostacyclin derivatives. Quantification of the efficiency of prostaglandin and thromboxane synthase-directed endoperoxide isomerization demonstrated that PGE, PGD, and PGI synthases catalyze the isomerization of PGH(2)-G at rates approaching those observed with PGH(2). In contrast, thromboxane synthase was far more efficient at catalyzing PGH(2) isomerization than at catalyzing the isomerization of PGH(2)-G. These results define the in vitro diversity of endocannabinoid-derived prostanoids and will permit focused investigations into their production and potential biological actions in vivo. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12244105/Metabolism_of_the_endocannabinoids_2_arachidonylglycerol_and_anandamide_into_prostaglandin_thromboxane_and_prostacyclin_glycerol_esters_and_ethanolamides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)71582-8 DB - PRIME DP - Unbound Medicine ER -