Online citations, reference lists, and bibliographies.
← Back to Search

Endocannabinoid Oxygenation By Cyclooxygenases, Lipoxygenases, And Cytochromes P450: Cross-Talk Between The Eicosanoid And Endocannabinoid Signaling Pathways

C. Rouzer, L. Marnett
Published 2011 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The discovery of the cannabinoid receptors CB1 and CB2 in 19881,2 and 1990,(3) respectively, and of the endogenous cannabinoid ligands (endocannabinoids) arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) in 1992(4) and 1995,(5) respectively, represented major strides in the understanding of cannabinoid physiology and pharmacology. The realization that both endocannabinoids are derivatives of arachidonic acid (AA) also revealed a potential interrelationship between the endocannabinoid and eicosanoid signaling systems that is just beginning to be unraveled. In this review, we explore what is known about the interplay between the two lipid signaling networks and discuss the challenges and opportunities offered by this new field of inquiry. 1.1. Eicosanoid Biosynthetic Pathways AA is an ω-6 tetraunsaturated fatty acid that is a component of mammalian cell membrane phospholipids, where it is predominantly esterified at the sn-2 position. AA’s role in eicosanoid signaling was first discovered in 1964, when Van Dorp et al. and Bergstrom et al. showed that incubation of the radiolabeled fatty acid with bull seminal vesicles led to the formation of prostaglandin E2 (PGE2).6,7 Since that time, we have come to appreciate that a wide range of stimuli (depending on cell type, tissue context, and physiologic state) can trigger the activation of cytosolic phospholipase A2 (cPLA2) and/or other phospholipases, leading to the release of free AA from phospholipid pools. The free fatty acid is then subject to oxidative metabolism by cyclooxygenase 1 and/or 2 (COX-1 and/or COX-2), leading to the formation of the endoperoxide PGH2. Tissue-specific metabolism of PGH2 by a group of PG synthases yields the biologically active PGs (PGE2, PGD2, PGF2α), prostacyclin (PGI2), and thromboxane A2 (TxA2) (Figure ​(Figure11a).8,9 Alternatively, free AA may be metabolized by one of a variety of lipoxygenases (LOXs) that catalyze regio- and stereospecific oxygenation, yielding hydro-peroxyeicosatetraenoic acids (HPETEs). These compounds are enzymatically or chemically reduced to the corresponding hydroxy-eicosatetraenoic acids (HETEs) or undergo further metabolism. Multiple lipoxygenations produce the lipoxins,(10) or in the case of 5-HPETE, epoxidation followed by hydrolysis or glutathione adduction yields the leukotrienes (LTs)9,11 (Figure ​(Figure1b).1b). Finally, free AA may be oxidized at each of its double bonds or at the ω-terminus by cytochromes P450, leading to the epoxyeicosatrienoic acids (EETs) or HETEs(12) (Figure ​(Figure1c).1c). Members of each of these classes of compounds possess a unique range of biological activities. Figure 1 (a) Cyclooxygenase pathway of AA metabolism. AA is converted to PGG2 at the cyclooxygenase active site of COX-1 or COX-2 and is then reduced to PGH2 at the peroxidase active site. PGH2 spontaneously decomposes to yield PGE2 or PGD2, but these compounds, ...
This paper references
Mol. Pharmacol
N T Snider (2009)
10.1016/J.PROSTAGLANDINS.2006.09.009
Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation.
H. Wang (2007)
10.1016/j.neuint.2010.10.018
Parecoxib and its metabolite valdecoxib directly interact with cannabinoid binding sites in CB1-expressing HEK 293 cells and rat brain tissue
H. Schroeder (2011)
10.1021/BI060163L
Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids.
D. Leung (2006)
Biochem. Biophys. Res. Commun
G Van Zadelhoff (1998)
10.1523/JNEUROSCI.4159-06.2007
Presynaptic Monoacylglycerol Lipase Activity Determines Basal Endocannabinoid Tone and Terminates Retrograde Endocannabinoid Signaling in the Hippocampus
Y. Hashimotodani (2007)
10.1523/JNEUROSCI.5693-09.2010
Loss of Retrograde Endocannabinoid Signaling and Reduced Adult Neurogenesis in Diacylglycerol Lipase Knock-out Mice
Y. Gao (2010)
Br. J. Pharmacol
L E Staniaszek (2010)
Br. J. Pharmacol
E Herrad On (2007)
Biochem. Pharmacol
C J Fowler (1241)
J. Biol. Chem. Arch. Biochem. Biophys
K R Kozak (2002)
10.1136/gut.2005.073403
The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2
H. Patsos (2005)
J. Proc. Natl. Acad. Sci. U.S.A
C S Nirodi (1840)
10.1074/jbc.M201084200
15-Lipoxygenase Metabolism of 2-Arachidonylglycerol
K. Kozak (2002)
10.1038/203461b0
Neuropharmacology
B. Rosner (1964)
10.1002/MC.20515
Metabolism of anandamide by COX-2 is necessary for endocannabinoid-induced cell death in tumorigenic keratinocytes.
R. Dross (2009)
10.1016/j.prostaglandins.2010.01.003
Structural determinants for calcium mobilization by prostaglandin E2 and prostaglandin F2alpha glyceryl esters in RAW 264.7 cells and H1819 cells.
Robyn Richie-Jannetta (2010)
J. Biol. Chem
A J Vecchio (2011)
10.1016/S0300-9084(97)83495-5
Structure and mechanism of lipoxygenases.
S. Prigge (1997)
10.1124/dmd.110.036707
Anandamide Oxidation by Wild-Type and Polymorphically Expressed CYP2B6 and CYP2D6
C. Sridar (2011)
10.1126/SCIENCE.294.5548.1871
Prostaglandins and leukotrienes: advances in eicosanoid biology.
C. Funk (2001)
10.1016/J.LFS.2006.08.017
Evaluation of the role of the arachidonic acid cascade in anandamide's in vivo effects in mice.
J. Wiley (2006)
J. Pharmacol. Exp. Ther
R A Ross (2002)
10.1016/J.CARDIORES.2004.03.024
2-Arachidonoyl glycerol induces contraction of isolated rat aorta: role of cyclooxygenase-derived products.
F. Stanke-Labesque (2004)
10.1038/sj.bjp.0706989
Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin‐ethanolamides) in the feline iris
D. Woodward (2007)
10.1074/jbc.M110.119867
Structural Basis of Fatty Acid Substrate Binding to Cyclooxygenase-2*
A. J. Vecchio (2010)
Eur. J. Pharmacol
H G€ Uhring (2002)
10.1124/dmd.110.033712
Effects of a Commonly Occurring Genetic Polymorphism of Human CYP3A4 (I118V) on the Metabolism of Anandamide
M. Pratt-Hyatt (2010)
10.1038/nn.2601
The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors
William R. Marrs (2010)
Biochim. Biophys. Acta
A J Hampson (1259)
10.1006/BBRC.1995.2437
2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.
T. Sugiura (1995)
10.1073/pnas.0909765106
Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1
G. Rimon (2009)
10.1016/j.jchromb.2009.05.024
Analysis of endocannabinoids, their congeners and COX-2 metabolites.
P. Kingsley (2009)
Biochim. Biophys. Acta
D A Dorp (1964)
10.1038/372686A0
Formation and inactivation of endogenous cannabinoid anandamide in central neurons
V. Marzo (1994)
10.1021/bi702530z
Oxidative metabolism of a fatty acid amide hydrolase-regulated lipid, arachidonoyltaurine.
Melissa V. Turman (2008)
10.1016/0014-5793(75)80439-X
A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria
T. Schewe (1975)
J. Pharmacol. Exp. Ther
D F Woodward (2003)
J. Biol. Chem
C Rouzer (2005)
10.1038/nri2294
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
C. Serhan (2008)
10.1042/BJ20071329
Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: possible involvement of the COX-2 metabolite prostamide E(2).
F. Corrêa (2008)
J. Thromb. Haemostasis
(2008)
10.1042/BJ20070289
Biosynthesis and metabolism of leukotrienes.
R. Murphy (2007)
10.1006/ABBI.1998.1025
Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.
C. Fowler (1999)
10.1194/jlr.R800042-JLR200
Cyclooxygenases: structural and functional insights Research on COX structure and function in the authors' laboratory is supported by grants from the National Institutes of Health (CA-89450 and GM-15431). Published, JLR Papers in Press, October 23, 2008.
C. Rouzer (2009)
Mechoulam, R.; Spatz, M. Circ. Res
Y Chen (2000)
10.1083/jcb.200305129
Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain
T. Bisogno (2003)
10.1016/0005-2760(94)00170-4
Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist.
N. Ueda (1995)
10.1074/jbc.M005722200
Anandamide Induces Apoptosis in Human Cells via Vanilloid Receptors
M. Maccarrone (2000)
10.1124/jpet.110.168831
Cyclooxygenase-2 Mediates Anandamide Metabolism in the Mouse Brain
S. Glaser (2010)
J. Pharmacol. Exp. Ther
I Matias (2004)
10.1016/J.ABB.2007.04.007
Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases.
J. J. Prusakiewicz (2007)
32) Schewe, T. Biol. Chem
(2002)
Arch. Biochem. Biophys
N Koda (2004)
10.1016/S0009-3084(02)00068-3
Chemical stability of 2-arachidonylglycerol under biological conditions.
C. Rouzer (2002)
10.1006/BBRC.1998.8910
With anandamide as substrate plant 5-lipoxygenases behave like 11-lipoxygenases.
G. van Zadelhoff (1998)
10.1016/0304-4165(64)90144-8
[The biosynthesis of prostaglandins].
H. Vonkeman (1966)
10.1016/J.BCP.2005.09.002
Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma.
B. Li (2005)
J. Pharmacol. Exp. Ther
N A Darmani (2002)
10.1124/JPET.301.3.900
Pharmacological characterization of the anandamide cyclooxygenase metabolite: prostaglandin E2 ethanolamide.
R. Ross (2002)
Mol. Carcinog
R T Dross (2009)
10.1036/1097-8542.554800
Psychopharmacology
B. Pitt (1968)
Prostaglandins Other Lipid Mediators
H Wang (2007)
10.1073/pnas.101119098
Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets
A. Berger (2001)
10.1038/bjp.2008.142
Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes
Y. Liang (2008)
10.1111/j.1476-5381.2010.00703.x
Effects of COX‐2 inhibition on spinal nociception: the role of endocannabinoids
L. E. Staniaszek (2010)
Biochem. Biophys. Res. Commun
T Sugiura (1995)
10.1007/s00213-003-1611-y
Anandamide inhibits the DOI-induced head-twitch response in mice
N. Egashira (2004)
Annu. Rev. Biochem. C. D. Science
B Samuelsson (1871)
10.1074/JBC.M105854200
Metabolism of Prostaglandin Glycerol Esters and Prostaglandin Ethanolamides in Vitro and in Vivo *
K. Kozak (2001)
10.1016/0005-2760(84)90113-9
Properties of canine myocardial phosphatidylethanolamine N-acyltransferase.
P. Reddy (1984)
10.1038/bjp.2008.33
Prostaglandin E2 glycerol ester, an endogenous COX‐2 metabolite of 2‐arachidonoylglycerol, induces hyperalgesia and modulates NFκB activity
S. Hu (2008)
10.1007/s00018-006-6445-4
Endocannabinoids in adipocytes during differentiation and their role in glucose uptake
V. Gasperi (2006)
J. Biochem. J
C A Rouzer (2006)
10.1074/jbc.272.34.21181
Synthesis of Prostaglandin E2 Ethanolamide from Anandamide by Cyclooxygenase-2*
M. Yu (1997)
Eur. J. Pharmacol
M Oz (2000)
10.1146/annurev.pharmtox.011008.145638
The COXIB experience: a look in the rearview mirror.
L. Marnett (2009)
10.1016/S0006-2952(99)00373-1
Pharmacological properties of rat brain fatty acid amidohydrolase in different subcellular fractions using palmitoylethanolamide as substrate.
G. Tiger (2000)
10.1124/JPET.102.047837
Pharmacological Characterization of a Novel Antiglaucoma Agent, Bimatoprost (AGN 192024)
D. Woodward (2003)
10.1016/j.mcn.2007.12.019
COX-2 oxidative metabolism of endocannabinoids augments hippocampal synaptic plasticity
H. Yang (2008)
10.1002/ijc.22761
Diverse roles of 2‐arachidonoylglycerol in invasion of prostate carcinoma cells: Location, hydrolysis and 12‐lipoxygenase metabolism
Michael P. Endsley (2007)
疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
宁北芳 (2005)
J. Physiol.: Heart Circ. Physiol
(1344)
10.1016/j.neuropharm.2008.04.018
Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain
M. Jhaveri (2008)
10.1146/ANNUREV.BIOCHEM.69.1.145
Cyclooxygenases: structural, cellular, and molecular biology.
W. Smith (2000)
Eur. J. Biochem. J. Neurosci. Res
T Sugiura (1226)
C. Mol. Pharmacol
W A Devane (1988)
Eur. J. Neurosci
M Ates (2003)
10.1021/BI0608008
A FAAH-regulated class of N-acyl taurines that activates TRP ion channels.
A. Saghatelian (2006)
Determination and characterization of a cannabinoid receptor in rat brain.
W. Devane (1988)
10.1152/AJPHEART.1995.269.6.H1859
Anandamide and delta 9-THC dilation of cerebral arterioles is blocked by indomethacin.
E. Ellis (1995)
10.1194/jlr.R800038-JLR200
Arachidonic acid cytochrome P450 epoxygenase pathway Work from my laboratory cited in this review was supported by National Institutes of Health grants HL049264 and HL072845. Published, JLR Papers in Press, October 23, 2008.
A. Spector (2009)
J. Biol. Chem
B Yan (1995)
10.1111/j.1742-4658.2008.06518.x
Expression and purification of orphan cytochrome P450 4X1 and oxidation of anandamide
Katarina Stark (2008)
10.1111/J.1432-1033.1996.0053H.X
Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine.
T. Sugiura (1996)
Prostaglandins Other Lipid Mediators
J Wang (2009)
Int. J. Oncol
H A Patsos (2010)
J. Biol. Chem
(2004)
10.1111/j.1476-5381.2009.00363.x
Factors influencing the regional haemodynamic responses to methanandamide and anandamide in conscious rats
S. Gardiner (2009)
10.1016/0006-291X(85)90453-X
Oxygenation of phosphatidylcholine by human polymorphonuclear leukocyte 15-lipoxygenase.
G. Jung (1985)
J. Cancer
(2007)
Br. J. Pharmacol
D F Woodward (2007)
J. Biol. Chem
Y Yu (1498)
Prostaglandins Other Lipid Mediators
J H Capdevila (2002)
10.1084/jem.20070828
COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARδ activation
M. Ghosh (2007)
J. Pharmacol. Exp. Ther
(2007)
10.1016/j.prostaglandins.2008.12.002
Biology of endocannabinoid synthesis system.
J. Wang (2009)
10.1074/jbc.M709873200
Identification of Novel Endogenous Cytochrome P450 Arachidonate Metabolites with High Affinity for Cannabinoid Receptors*
J. Chen (2008)
S29. (46) Smith
C A Rouzer (2000)
J. Biol. Chem
C Yuan (2009)
Br. J. Pharmacol
D.-S Burk (1538)
10.1038/oby.2009.177
Anandamide Increases the Differentiation of Rat Adipocytes and Causes PPARγ and CB1 Receptor Upregulation
S. Karaliota (2009)
10.1136/bmj.1.4959.155-a
Biochemistry
F. G. Young (1955)
J. Biochem. Biophys. Res. Commun
J J Prusakiewicz (2002)
10.1016/j.pharmthera.2008.08.001
The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products.
D. Woodward (2008)
Prostaglandins Other Lipid Media
J. H. Capdevila (2001)
Chem. Biol
J L Blankman (1347)
10.1124/jpet.107.119321
Anandamide Metabolism by Human Liver and Kidney Microsomal Cytochrome P450 Enzymes to Form Hydroxyeicosatetraenoic and Epoxyeicosatrienoic Acid Ethanolamides
Natasha T Snider (2007)
Prostaglandins Other Lipid Mediators
R Richie-Jannetta (2010)
Biochim. Biophys. Acta
N Ueda (1254)
J. Biol. Chem. C. A.; Marnett, L. J. Chem. Rev
R Yang (2003)
10.1074/JBC.M104467200
Amino Acid Determinants in Cyclooxygenase-2 Oxygenation of the Endocannabinoid 2-Arachidonylglycerol*
K. Kozak (2001)
10.1016/S0014-2999(02)01650-3
Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of longitudinal smooth muscle from the guinea-pig distal colon in vitro.
S. Kojima (2002)
Biochem. Pharmacol. Biochim. Biophys. Acta
B Li (1673)
10.1016/j.neuropharm.2005.04.019
Inhibition of cyclooxygenase-2 elicits a CB1-mediated decrease of excitatory transmission in rat CA1 hippocampus
K. Slanina (2005)
10.1074/jbc.273.10.5801
The Dynamics of Prostaglandin H Synthases
O. Y. So (1998)
10.1523/JNEUROSCI.17-04-01226.1997
Occurrence and Biosynthesis of Endogenous Cannabinoid Precursor,N-Arachidonoyl Phosphatidylethanolamine, in Rat Brain
H. Cadas (1997)
Annu. Rev. Biochem. Chem. Res. Toxicol
M K Mckinney (1890)
10.1371/journal.pone.0010628
R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids
P. Bishay (2010)
10.1046/j.1460-9568.2003.02470.x
Intrathecally applied flurbiprofen produces an endocannabinoid‐dependent antinociception in the rat formalin test
M. Ates (2003)
10.1124/JPET.103.061705
Prostaglandin Ethanolamides (Prostamides): In Vitro Pharmacology and Metabolism
I. Matias (2004)
J. Biol. Chem
K R Kozak (2001)
10.1016/J.BCP.2005.01.016
Cyclooxygenation of the arachidonoyl side chain of 1-arachidonoylglycerol and related compounds block their ability to prevent anandamide and 2-oleoylglycerol metabolism by rat brain in vitro.
C. Fowler (2005)
Br. J. Pharmacol
H.-P Cornell (1079)
Biochim. Biophys. Acta
J L Wiley (1394)
J. Pharmacol
(1143)
Biochem. Biophys. Res. Commun
G Jung (1985)
Neurochem. Int. Biochemistry
H Schr€ Oder (2009)
10.1016/j.neuropharm.2005.04.021
Endocannabinoids restrict hippocampal long-term potentiation via CB1
K. Slanina (2005)
Cannabinoid receptor binding and agonist activity of amides and esters of arachidonic acid.
J. Pinto (1994)
10.1016/j.otohns.2009.05.016
Nature
R. Rosenfeld (2009)
J. Biol. Chem
A J Vecchio (2010)
J. Exp. Med. Biochem. Pharmacol
M Ghosh (2007)
10.1038/346561A0
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
L. Matsuda (1990)
10.1124/mol.108.053439
A Cytochrome P450-Derived Epoxygenated Metabolite of Anandamide Is a Potent Cannabinoid Receptor 2-Selective Agonist
Natasha T Snider (2009)
10.1021/tx1002194
Inactivation of lipid glyceryl ester metabolism in human THP1 monocytes/macrophages by activated organophosphorus insecticides: role of carboxylesterases 1 and 2.
S. Xie (2010)
J. Biol. Chem
K R Kozak (2001)
J. Pharmacol. Exp. Ther
S T Glaser (2010)
10.1073/pnas.0303950101
The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells
C. Nirodi (2004)
Eur. J. Pharmacol
S Kojima (2002)
10.1016/0304-4165(64)90145-X
THE ENZYMATIC FORMATION OF PROSTAGLANDIN E2 FROM ARACHIDONIC ACID PROSTAGLANDINS AND RELATED FACTORS 32.
S. Bergstroem (1964)
10.1074/jbc.M007088200
Oxygenation of the Endocannabinoid, 2-Arachidonylglycerol, to Glyceryl Prostaglandins by Cyclooxygenase-2*
K. Kozak (2000)
10.1074/jbc.M111.230367
The Structural Basis of Endocannabinoid Oxygenation by Cyclooxygenase-2*
A. J. Vecchio (2011)
10.1126/SCIENCE.1470919
Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
W. Devane (1992)
Mol. Cell. Biol. Chemical Reviews REVIEW J. R.; Kearn, C. S.; Campbell, W. B. Mol. Pharmacol
J Chen (1998)
10.1021/BI002303B
Selective oxygenation of the endocannabinoid 2-arachidonylglycerol by leukocyte-type 12-lipoxygenase.
J. Moody (2001)
10.1074/JBC.M206788200
Metabolism of the Endocannabinoids, 2-Arachidonylglycerol and Anandamide, into Prostaglandin, Thromboxane, and Prostacyclin Glycerol Esters and Ethanolamides*
K. Kozak (2002)
10.1042/BJ20060615
Zymosan-induced glycerylprostaglandin and prostaglandin synthesis in resident peritoneal macrophages: roles of cyclo-oxygenase-1 and -2.
C. Rouzer (2006)
10.1111/j.1538-7836.2008.03093.x
The endocannabinoid 2‐arachidonoylglycerol activates human platelets through non‐CB1/CB2 receptors
S. Baldassarri (2008)
Nat. Neurosci
W R Marrs (2010)
10.1146/ANNUREV.BIOCHEM.74.082803.133450
Structure and function of fatty acid amide hydrolase.
M. K. McKinney (2005)
10.1074/jbc.M808634200
Cyclooxygenase Allosterism, Fatty Acid-mediated Cross-talk between Monomers of Cyclooxygenase Homodimers*
C. Yuan (2009)
10.1007/112_0505
Endocannabinoids: synthesis and degradation.
V. Marzo (2006)
10.1124/JPET.300.1.34
The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannnabinoids.
N. Darmani (2002)
Annu. Rev. Pharmacol. Toxicol. J. Biol. Chem. J. Biol. Chem
L J Marnett (1997)
10.1016/j.pain.2009.08.013
Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: Involvement of prostaglandins and endocannabinoids
A. Telleria-Diaz (2010)
10.1016/J.CHEMBIOL.2007.11.006
A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.
J. Blankman (2007)
Physiol. Biochem. Pharmacol. J. Cell Biol
Di Marzo (2003)
10.1016/J.EJPHAR.2007.02.051
Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin.
S. Holt (2007)
J. Lipid Res
R C Murphy (2007)
10.1074/jbc.M111.237990
Decoding Functional Metabolomics with Docosahexaenoyl Ethanolamide (DHEA) Identifies Novel Bioactive Signals*
R. Yang (2011)
10.1021/JM020818Q
Oxygenated metabolites of anandamide and 2-arachidonoylglycerol: conformational analysis and interaction with cannabinoid receptors, membrane transporter, and fatty acid amide hydrolase.
M. van der Stelt (2002)
Cell. Mol. Life Sci
V Gasperi (2007)
10.1074/jbc.M609930200
Targeted Cyclooxygenase Gene (Ptgs) Exchange Reveals Discriminant Isoform Functionality*
Y. Yu (2007)
10.1016/S0014-2999(00)00396-4
Endogenous cannabinoid anandamide directly inhibits voltage-dependent Ca(2+) fluxes in rabbit T-tubule membranes.
M. Oz (2000)
10.1021/BI7005898
Hydrolysis of prostaglandin glycerol esters by the endocannabinoid-hydrolyzing enzymes, monoacylglycerol lipase and fatty acid amide hydrolase.
A. Vila (2007)
10.1038/365061A0
Molecular characterization of a peripheral receptor for cannabinoids
S. Munro (1993)
J. Chem. Phys. Lipids
C A Rouzer (2002)
10.1016/0891-5849(94)90149-X
Regio- and stereochemistry of the dioxygenation reaction catalyzed by (S)-type lipoxygenases or by the cyclooxygenase activity of prostaglandin H synthases.
W. D. Lehmann (1994)
10.1128/MCB.01482-06
Mitogenic Activity and Signaling Mechanism of 2-(14,15- Epoxyeicosatrienoyl)Glycerol, a Novel Cytochrome P450 Arachidonate Metabolite
J. Chen (2007)
J. J. Biol. Chem
K R Kozak (2002)
10.1124/MOL.54.1.180
Human platelets and polymorphonuclear leukocytes synthesize oxygenated derivatives of arachidonylethanolamide (anandamide): their affinities for cannabinoid receptors and pathways of inactivation.
W. Edgemond (1998)
10.1007/978-94-007-2150-0_9030
Nature of Science
Xie Hong-kun (2002)
10.1074/JBC.270.32.19128
Rat Serum Carboxylesterase
B. Yan (1995)
10.1152/AJPHEART.00718.2005
The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs.
H. Wahn (2005)
10.7326/0003-4819-149-7-200810070-01004
Obesity
G. Bray (2008)
10.1515/BC.2002.041
15-Lipoxygenase-1: A Prooxidant Enzyme
T. Schewe (2002)
Gut Biochem. J. Chemical Reviews REVIEW Pharmacol. Toxicol
H A Patsos (1741)
J. W. Pharmacol. Ther
D F Woodward (2008)
J. Med. Chem
M Van Der Stelt (2002)
Finazzi-Agro, A. J. Biol. Chem
M Maccarrone (2000)
Arch. Biochem. Biophys
C J Fowler (1999)
Nat. Chem. Biol. Nat. Chem. Biol
J Z Long (2008)
10.1074/jbc.M306642200
Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners*
Y. Okamoto (2004)
J. Neurochem
M Oz (1454)
10.1016/S0006-291X(02)00915-4
Selective oxygenation of N-arachidonylglycine by cyclooxygenase-2.
J. J. Prusakiewicz (2002)
10.3892/IJO_00000666
The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells.
H. Patsos (2010)
10.1124/JPET.104.065524
A Cyclooxygenase Metabolite of Anandamide Causes Inhibition of Interleukin-2 Secretion in Murine Splenocytes
C. Rockwell (2004)
Mol. Pharmacol
J C Pinto (1994)
10.1146/ANNUREV.BI.47.070178.005025
PROSTAGLANDINS AND THROMBOXANES
M. Caton (1977)
J. Pharmacol. Exp. Ther
C E Rockwell (2004)
10.1111/J.1600-0773.1997.TB00291.X
Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide.
C. Fowler (1997)
10.1016/0006-2952(95)00177-2
Microsomal cytochrome P450-mediated liver and brain anandamide metabolism.
L. Bornheim (1995)
10.1016/S0014-5793(97)00718-7
Dioxygenation of N‐linoleoyl amides by soybean lipoxygenase‐1
M. van der Stelt (1997)
Biochem. Pharmacol
L M Bornheim (1995)
10.1016/S0014-5793(97)01148-4
The effect of hydroxylation of linoleoyl amides on their cannabinomimetic properties
M. van der Stelt (1997)
10.1161/01.RES.87.4.323
Human Brain Capillary Endothelium: 2-Arachidonoglycerol (Endocannabinoid) Interacts With Endothelin-1
Y. Chen (2000)
10.1016/0306-4522(80)90014-7
Pain
J. Priestley (1980)
10.1016/j.bcp.2008.05.005
A COX-2 metabolite of the endogenous cannabinoid, 2-arachidonyl glycerol, mediates suppression of IL-2 secretion in activated Jurkat T cells.
C. Rockwell (2008)
Acta
(1964)
10.1113/jphysiol.2006.105569
PGE2 glycerol ester, a COX‐2 oxidative metabolite of 2‐arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons
N. Sang (2006)
10.1021/CR000068X
Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases.
C. Rouzer (2003)
10.1016/S0014-2999(02)02485-8
A role for endocannabinoids in indomethacin-induced spinal antinociception.
H. Gühring (2002)
J. Biol. Chem
O Y So (1998)
10.1038/nn.2616
Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system
J. Schlosburg (2010)
Free Radical Biol. Med
W D Lehmann (1975)
Biochimie
S Prigge (1997)
10.1038/nchembio.86
Activation of the endocannabinoid system by organophosphorus nerve agents.
Daniel K. Nomura (2008)
J. Biochem. Pharmacol
G Tiger (2000)
10.1111/j.1471-4159.2009.06557.x
The endogenous cannabinoid, anandamide, inhibits dopamine transporter function by a receptor‐independent mechanism
M. Oz (2010)
J. Physiol
N Sang (2006)
Am. J. Physiol
E F Ellis (1995)
J. Biol. Chem
J.-K Chen (2008)
10.4324/9781315803241
Neuroscience 細胞死:最近の知見
廣瀬雄一 (2010)
10.1038/sj.bjp.0707404
Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta
E. Herradón (2007)
10.1038/nchembio.129
Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
J. Z. Long (2009)
10.1194/JLR.M300475-JLR200
Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry Published, JLR Papers in Press, January 16, 2004. DOI 10.1194/jlr.M300475-JLR200
A. Weber (2004)
10.1074/JBC.M501021200
Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus*
C. Rouzer (2005)
10.1016/S0005-2760(98)00110-6
Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system.
V. K. Pestonjamasp (1998)
10.1038/nn1262
Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus
J. Kim (2004)
10.1021/bi900999z
Differential Sensitivity and Mechanism of Inhibition of COX-2 Oxygenation of Arachidonic Acid and 2-Arachidonoylglycerol by Ibuprofen and Mefenamic Acid†
J. J. Prusakiewicz (2009)
Drug Metab. Dispos
C Sridar (2011)
10.1016/j.neuroscience.2009.06.004
Cannabinoid signaling in inhibitory autaptic hippocampal neurons
A. Straiker (2009)
10.1016/J.ABB.2004.02.009
Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and identification of Bimatoprost as a potent inhibitor of the enzyme: new enzyme assay method using LC/ESI/MS.
N. Koda (2004)
10.1016/0005-2760(95)00157-8
Anandamide hydroxylation by brain lipoxygenase:metabolite structures and potencies at the cannabinoid receptor.
A. Hampson (1995)
C. Mol. Cell. Neurosci
H Yang (2008)
Cardiovasc. Res
F Stanke-Labesque (2004)
10.1016/S0090-6980(02)00038-2
Biochemical and molecular properties of the cytochrome P450 arachidonic acid monooxygenases.
J. Capdevila (2002)
Drug Metab. Dispos
M Pratt-Hyatt (2010)
Review article biosynthesis and metabolism of leukotrienes
R. Murphy (2007)
10.1016/S0304-3940(02)01366-6
Flurbiprofen inhibits capsaicin induced calcitonin gene related peptide release from rat spinal cord via an endocannabinoid dependent mechanism
K. Seidel (2003)
J.Chromatogr., B: Anal. Technol. Biomed. Life Sci.
C. Deng (2004)
10.1152/AJPHEART.00537.2004
Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries.
K. M. Gauthier (2005)
Nat. Rev. Immunol
C N Serhan (2008)



This paper is referenced by
10.1038/nchem.1924
mitochondrial pathway for biosynthesis of lipid mediators
Y. Tyurina (2014)
10.1039/c3cc43447h
Isolation of a Mn(IV) acylperoxo complex and its monooxidation ability.
Takahiro Kikunaga (2013)
10.1007/s11745-016-4144-y
Brain 2-Arachidonoylglycerol Levels Are Dramatically and Rapidly Increased Under Acute Ischemia-Injury Which Is Prevented by Microwave Irradiation
Stephen A. Brose (2016)
Endocannabinoid system and placentaldevelopment: importance in trophoblast cellular turnover and modulation of protein expression
M. Costa (2014)
10.1007/s13277-013-0672-8
The association between cyclooxygenase-2 1195 G/A polymorphism and hepatocellular carcinoma: evidence from a meta-analysis
Xianmin Bu (2013)
10.1074/jbc.TM118.006295
Interactions of fatty acids, nonsteroidal anti-inflammatory drugs, and coxibs with the catalytic and allosteric subunits of cyclooxygenases-1 and -2
W. Smith (2019)
10.1002/hep.30929
Monoacylglycerol Lipase Inhibition Protects From Liver Injury in Mouse Models of Sclerosing Cholangitis
M. Tardelli (2019)
10.1074/jbc.RA119.007405
Fluorescent indomethacin-dansyl conjugates utilize the membrane-binding domain of cyclooxygenase-2 to block the opening to the active site
Shu 曙 Xu 徐 (2019)
10.1074/jbc.M115.668038
A Revised Mechanism for Human Cyclooxygenase-2*
Yi Liu (2015)
10.1371/journal.pone.0109869
Biochemical and Pharmacological Characterization of the Human Lymphocyte Antigen B-Associated Transcript 5 (BAT5/ABHD16A)
J. Savinainen (2014)
10.1039/c7ob02992f
Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide.
J. Qiao (2018)
10.1074/jbc.M117.783068
The phospholipase iPLA2γ is a major mediator releasing oxidized aliphatic chains from cardiolipin, integrating mitochondrial bioenergetics and signaling
Gao-Yuan Liu (2017)
10.1002/9780470015902.A0023205
Cyclooxygenase-2: Biology of Prostanoid Biosynthesis and Metabolism
Paola Patrignani (2012)
10.1111/nyas.12081
Lipids and addiction: how sex steroids, prostaglandins, and cannabinoids interact with drugs of abuse
E. Leishman (2013)
10.1016/j.neuropharm.2013.03.021
Anandamide deficiency and heightened neuropathic pain in aged mice
P. Bishay (2013)
10.1007/978-3-319-06151-1_9
The Endocannabinoid System: A Dynamic Signalling System at the Crossroads Between Metabolism and Disease
R. Witkamp (2014)
10.1155/2014/169203
Peripheral Blood Mononuclear Cells as a Laboratory to Study Dementia in the Elderly
B. Arosio (2014)
Fatty Acid Amides and Their Biosynthetic Enzymes Found in Insect Model Systems
R. L. Anderson (2018)
Knockdown of Delta-5 Desaturase to Elicit Anti-Cancer Effect of Dihomo-γ-Linolenic Acid: Development of an ω-6 Fatty Acid-Based Therapeutic Strategy for Pancreatic Cancer
X. Yang (2017)
10.1021/ml3001616
Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes
Matthew A. Windsor (2012)
10.1111/febs.12125
Epigenetic mechanisms and endocannabinoid signalling
C. D'Addario (2013)
10.3389/fnins.2017.00293
Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review
M. Koch (2017)
10.3389/fnmol.2018.00436
Broad and Region-Specific Impacts of the Synthetic Cannabinoid CP 55,940 in Adolescent and Adult Female Mouse Brains
E. Leishman (2018)
10.1016/j.bbalip.2015.08.011
Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator.
M. Almada (2015)
SEX STEROID HORMONE INFLUENCE ON ENDOCANNABINOID SYSTEM IN THE FEMALE REPRODUCTIVE TRACT
G. Correia-da-Silva (2016)
10.1073/pnas.1610325114
Anti-inflammatory ω-3 endocannabinoid epoxides
Daniel R. McDougle (2017)
10.1016/j.phrs.2013.12.010
Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice.
S. Nicolussi (2014)
10.1007/s40261-016-0379-x
Plant-Derived and Endogenous Cannabinoids in Epilepsy
A. Verrotti (2016)
10.1042/EBC20190086
The endocannabinoid system.
Aruna Kilaru (2020)
10.1002/9781118451281.CH3
Endocannabinoid biochemistry: What do we know after 50 years?
F. Fezza (2014)
10.1080/13543784.2016.1236913
Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas
A. I. Fraguas-Sánchez (2016)
10.1111/bph.12030
N‐acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads
J. Meijerink (2013)
See more
Semantic Scholar Logo Some data provided by SemanticScholar