Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides
Open accessAbstract
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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COX-2 utilizes 2-AG and AEA as substrates to generate prostaglandin-glycerol (PG-G) and prostaglandin ethanolamide (PG-EA), respectively.
“has also been shown to utilize 2-AG and AEA as substrates to generate prostaglandin-glycerol (PG-G) and prostaglandin ethanolamide (PG-EA), respectively (Kozak et al., 2002; Kozak et al., 2000).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Kozak et al., 2002
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References 47 · Cited by 368
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- Authors
- Kozak, K. R., Crews, B. C., Morrow, J. D., Wang, L.-H., Ma, Y. H., Weinander, R., Jakobsson, P.-J., & Marnett, L. J.
- Affiliations
- Vanderbilt University (US)
- Karolinska Institutet (SE)
- Corresponding author
- Marnett, Lawrence J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 277
- Issue
- 47
- Pages
- 44877-44885
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2049772907
- Cited by
- 368
- References
- 47
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 9 · 2019: 14 · 2018: 11 · 2017: 14 · 2016: 17 · 2015: 22 · 2014: 34 · 2013: 19 · 2012: 20
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (ES00267, GM 15431, CA 77839)
- National Cancer Institute (R01CA089450, CA89450, CA 68484, CA77839, P01CA077839, P01CA068484)
- National Institute of General Medical Sciences (GM 15431, GM 07347, T32GM007347)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 48831, R01DK048831)
- National Institute of Environmental Health Sciences (ES00267)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endocannabinoids, 2-arachidonoylglycerol, anandamide, cyclooxygenase-2, thromboxane synthase, prostacyclin synthase, prostaglandin H2, prostanoid metabolism
- MeSH terms
- Animals, Aorta, Arachidonic Acids, Cannabinoids, Cattle, Cell Line, Esters, Glycerides, Glycerol, Humans, Isoenzymes, Membrane Proteins, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Epoprostenol, Stereoisomerism, Thromboxane-A Synthase, Thromboxanes, Molecular Structure, Neurotransmitter Agents, Intramolecular Oxidoreductases, Mice, Cyclooxygenase 2, Polyunsaturated Alkamides, Lipocalins, Cannabinoid Receptor Modulators, Endocannabinoids
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