The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Oxygenation of the Endocannabinoid, 2-Arachidonylglycerol, to Glyceryl Prostaglandins by Cyclooxygenase-2
Open accessAbstract
Cyclooxygenases (COX) play an important role in lipid signaling by oxygenating arachidonic acid to endoperoxide precursors of prostaglandins and thromboxane. Two cyclooxygenases exist which differ in tissue distribution and regulation but otherwise carry out identical chemical functions. The neutral arachidonate derivative, 2-arachidonylglycerol (2-AG), is one of two described endocannabinoids and appears to be a ligand for both the central (CB1) and peripheral (CB2) cannabinoid receptors. Here we report that 2-AG is a substrate for COX-2 and that it is metabolized as effectively as arachidonic acid. COX-2-mediated 2-AG oxygenation provides the novel lipid, prostaglandin H(2) glycerol ester (PGH(2)-G), in vitro and in cultured macrophages. PGH(2)-G produced by macrophages is a substrate for cellular PGD synthase, affording PGD(2)-G. Pharmacological studies reveal that macrophage production of PGD(2)-G from endogenous sources of 2-AG is calcium-dependent and mediated by diacylglycerol lipase and COX-2. These results identify a distinct function for COX-2 in endocannabinoid metabolism and in the generation of a new family of prostaglandins derived from diacylglycerol and 2-AG.
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“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., 2000
Citations
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Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
Long, J. Z., Li, W., Booker, L., Burston, J. J., Kinsey, S. G., Schlosburg, J. E., Pavón, F. J., Serrano, A., Selley, D. E., Parsons, L. H., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.129 · Cited by 954
ENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
Chevaleyre, V., Takahashi, K. A., & Castillo, P. E. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112834 · Cited by 829
Multiple Functions of Endocannabinoid Signaling in the Brain
Katona, I., & Freund, T. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150420 · Cited by 630
Why there are two cyclooxygenase isozymes
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Metadata
- Authors
- Kozak, K. R., Rowlinson, S. W., & Marnett, L. J.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Marnett, Lawrence J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 43
- Pages
- 33744-33749
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2086458197
- Cited by
- 390
- References
- 44
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 18 · 2021: 13 · 2020: 16 · 2019: 14 · 2018: 10 · 2017: 17 · 2016: 18 · 2015: 15 · 2014: 16 · 2013: 19 · 2012: 18
- FWCI
- 8.84
- 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 (5r35ca047479-10)
- National Cancer Institute (CA-47479, CA 68484, P01CA068484)
- National Institute of Environmental Health Sciences (ES00267)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- 2-arachidonoylglycerol, endocannabinoids, cyclooxygenase-2, endocannabinoid metabolism, macrophages, diacylglycerol lipase, lipid signaling, arachidonic acid oxygenation
- MeSH terms
- Animals, Arachidonic Acids, Binding Sites, Cell Line, Glycerides, Humans, Isoenzymes, Male, Membrane Proteins, Prostaglandin-Endoperoxide Synthases, Sheep, Prostaglandin D2, Mice, Cyclooxygenase 1, Cyclooxygenase 2, Cannabinoid Receptor Modulators, Endocannabinoids
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