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Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases.
Biochim Biophys Acta. 2015 Apr; 1851(4):366-76.BB

Abstract

The naturally occurring mammalian endocannabinoids possess biological attributes that extend beyond interaction with cannabinoid receptors. These extended biological properties are the result of oxidative metabolism of the principal mammalian endocannabinoids arachidonoyl ethanolamide (anandamide; A-EA) and 2-arachidonoylglycerol (2-AG). Both endocannabinoids are oxidized by cyclo-oxygenase-2 (COX-2), but not by COX-1, to a series of prostaglandin derivatives (PGs) with quite different biological properties from those of the parent substrates. PG ethanolamides (prostamides, PG-EAs) and PG glyceryl esters (PG-Gs) are not only pharmacologically distinct from their parent endocannabinoids, they are distinct from the corresponding acidic PGs, and are differentiated from each other. Ethanolamides and glyceryl esters of the major prostanoids PGD2, PGE2, PGF2α, and PGI2 are formed by the various PG synthases, and thromboxane ethanolamides and glyceryl esters are not similarly produced. COX-2 is also of interest by virtue of its corollary central role in modulating endocannabinoid tone, providing a new therapeutic approach for treating pain and anxiety. Other major oxidative conversion pathways are provided for both A-EA and 2-AG by several lipoxygenases (LOXs), resulting in the formation of numerous hydroxyl metabolites. These do not necessarily represent inactivation pathways for endocannabinoids but may mimic or modulate the endocannabinoids or even display alternative pharmacology. Similarly, A-EA and 2-AG may be oxidized by P450 enzymes. Again a very diverse number of metabolites are formed, with either cannabinoid-like biological properties or an introduction of disparate pharmacology. The biological activity of epoxy and hydroxyl derivatives of the endocannabinoids remains to be fully elucidated. This review attempts to consolidate and compare the findings obtained to date in an increasingly important research area. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

Authors+Show Affiliations

Manchester Pharmacy School, Faculty of Medical and Human Sciences, Stopford Building, Oxford Road, The University of Manchester, M13 9PT, UK.Manchester Pharmacy School, Faculty of Medical and Human Sciences, Stopford Building, Oxford Road, The University of Manchester, M13 9PT, UK. Electronic address: anna.nicolaou@manchester.ac.uk.Dept of Biological Sciences, Allergan, Inc., Irvine, CA 92612, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

25543004

Citation

Urquhart, P, et al. "Endocannabinoids and Their Oxygenation By Cyclo-oxygenases, Lipoxygenases and Other Oxygenases." Biochimica Et Biophysica Acta, vol. 1851, no. 4, 2015, pp. 366-76.
Urquhart P, Nicolaou A, Woodward DF. Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases. Biochim Biophys Acta. 2015;1851(4):366-76.
Urquhart, P., Nicolaou, A., & Woodward, D. F. (2015). Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases. Biochimica Et Biophysica Acta, 1851(4), 366-76. https://doi.org/10.1016/j.bbalip.2014.12.015
Urquhart P, Nicolaou A, Woodward DF. Endocannabinoids and Their Oxygenation By Cyclo-oxygenases, Lipoxygenases and Other Oxygenases. Biochim Biophys Acta. 2015;1851(4):366-76. PubMed PMID: 25543004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases. AU - Urquhart,P, AU - Nicolaou,A, AU - Woodward,D F, Y1 - 2014/12/24/ PY - 2014/10/08/received PY - 2014/12/09/revised PY - 2014/12/16/accepted PY - 2014/12/28/entrez PY - 2014/12/30/pubmed PY - 2015/9/9/medline KW - 2-Arachidonyl glycerol ester KW - Anandamide KW - Cyclo-oxygenase-2 KW - Cytochrome P450 oxygenase KW - Lipoxygenase KW - Prostaglandin glyceryl ester KW - Prostamide SP - 366 EP - 76 JF - Biochimica et biophysica acta JO - Biochim Biophys Acta VL - 1851 IS - 4 N2 - The naturally occurring mammalian endocannabinoids possess biological attributes that extend beyond interaction with cannabinoid receptors. These extended biological properties are the result of oxidative metabolism of the principal mammalian endocannabinoids arachidonoyl ethanolamide (anandamide; A-EA) and 2-arachidonoylglycerol (2-AG). Both endocannabinoids are oxidized by cyclo-oxygenase-2 (COX-2), but not by COX-1, to a series of prostaglandin derivatives (PGs) with quite different biological properties from those of the parent substrates. PG ethanolamides (prostamides, PG-EAs) and PG glyceryl esters (PG-Gs) are not only pharmacologically distinct from their parent endocannabinoids, they are distinct from the corresponding acidic PGs, and are differentiated from each other. Ethanolamides and glyceryl esters of the major prostanoids PGD2, PGE2, PGF2α, and PGI2 are formed by the various PG synthases, and thromboxane ethanolamides and glyceryl esters are not similarly produced. COX-2 is also of interest by virtue of its corollary central role in modulating endocannabinoid tone, providing a new therapeutic approach for treating pain and anxiety. Other major oxidative conversion pathways are provided for both A-EA and 2-AG by several lipoxygenases (LOXs), resulting in the formation of numerous hydroxyl metabolites. These do not necessarily represent inactivation pathways for endocannabinoids but may mimic or modulate the endocannabinoids or even display alternative pharmacology. Similarly, A-EA and 2-AG may be oxidized by P450 enzymes. Again a very diverse number of metabolites are formed, with either cannabinoid-like biological properties or an introduction of disparate pharmacology. The biological activity of epoxy and hydroxyl derivatives of the endocannabinoids remains to be fully elucidated. This review attempts to consolidate and compare the findings obtained to date in an increasingly important research area. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/25543004/Endocannabinoids_and_their_oxygenation_by_cyclo_oxygenases_lipoxygenases_and_other_oxygenases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1388-1981(14)00267-4 DB - PRIME DP - Unbound Medicine ER -