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Anandamide Amidohydrolase Reacting With 2‐arachidonoylglycerol, Another Cannabinoid Receptor Ligand

S. Goparaju, N. Ueda, H. Yamaguchi, S. Yamamoto
Published 1998 · Chemistry, Medicine

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Two endogenous ligands for cannabinoid receptors, anandamide (arachidonylethanolamide) and 2‐arachidonoylglycerol, lose their biological activities by enzymatic hydrolysis. A cDNA for a rat liver enzyme hydrolyzing anandamide as well as oleamide was overexpressed in COS‐7 cells. When the particulate fraction was allowed to react with 2‐arachidonoylglycerol, arachidonic acid was produced. In contrast, this hydrolytic reaction did not occur with the control cells. The hydrolysis of 2‐arachidonoylglycerol proceeded about 4‐fold faster than the anandamide hydrolysis with a K m value as low as 6 μM and an optimal pH of 10. Phenylmethylsulfonyl fluoride and methyl arachidonyl fluorophosphonate inhibited the hydrolysis of both anandamide and 2‐arachidonoylglycerol in parallel. Furthermore, the hydrolysis of [14C]2‐arachidonoylglycerol was inhibited by anandamide dose‐dependently. These results suggest that anandamide and 2‐arachidonoylglycerol can be inactivated by the same enzyme.
This paper references
Comprehensive organic chemistry : the synthesis and reactions of organic compounds
D. Barton (1978)
Methyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase.
D. Deutsch (1997)
Comprehensive Organic Chemistry (Barton
F. D. Gunstone (1979)
Some properties of a lipase from Rhizopus arrhizus. Separation of a glycopeptide bound to the enzyme.
M. Sémériva (1969)
Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase.
Y. Kurahashi (1997)
Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids.
K. Watanabe (1996)
Monoglyceride and diglyceride lipases from human platelet microsomes.
L. Chau (1988)
Biosynthesis, Uptake, and Degradation of Anandamide and Palmitoylethanolamide in Leukocytes*
T. Bisogno (1997)
Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
W. Devane (1992)
Metabolism of anandamide, an endogenous cannabinoid receptor ligand, in porcine ocular tissues.
S. Matsuda (1997)
Two novel classes of neuroactive fatty acid amides are substrates for mouse neuroblastoma ‘anandamide amidohydrolase’
S. Maurelli (1995)
A second endogenous cannabinoid that modulates long-term potentiation
N. Stella (1997)
Purification and properties of a monoacylglycerol lipase in human erythrocytes.
C. Somma-Delpero (1995)
2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.
T. Sugiura (1995)
Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain.
C. Hillard (1995)
Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells.
T. Bisogno (1997)
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
M. M. Bradford (1976)
Characterization of 1,2-diacylglycerol hydrolysis in human platelets. Demonstration of an arachidonoyl-monoacylglycerol intermediate.
S. Prescott (1983)
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
R. Mechoulam (1995)
Arachidonic acid release from diacylglycerol in human neutrophils. Translocation of diacylglycerol-deacylating enzyme activities from an intracellular pool to plasma membrane upon cell activation.
J. Balsinde (1991)
Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine.
K. Katayama (1997)
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
B. Cravatt (1996)
Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist.
D. Deutsch (1993)
Molecular aspects of cannabinoid receptors.
L. Matsuda (1997)
Novel inhibitors of brain, neuronal, and basophilic anandamide amidohydrolase.
L. De Petrocellis (1997)
Identity of purified monoacylglycerol lipase, palmitoyl-CoA hydrolase and aspirin-metabolizing carboxylesterase from rat liver microsomal fractions. A comparative study with enzymes purified in different laboratories.
R. Mentlein (1985)
Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist.
N. Ueda (1995)
Pharmacology of cannabinoid CB1 and CB2 receptors.
R. Pertwee (1997)
The uterus is a potential site for anandamide synthesis and hydrolysis: Differential profiles of anandamide synthase and hydrolase activities in the mouse uterus during the periimplantation period
B. Paria (1996)
Diglyceride/monoglyceride lipases pathway is not essential for arachidonate release in thrombin-activated human platelets.
L. Chau (1983)
Specificity of purified monoacylglycerol lipase, palmitoyl-CoA hydrolase, palmitoyl-carnitine hydrolase, and nonspecific carboxylesterase from rat liver microsomes.
R. Mentlein (1984)
Partial Purification and Characterization of the Porcine Brain Enzyme Hydrolyzing and Synthesizing Anandamide (*)
N. Ueda (1995)
Resolution of hormone-sensitive triglyceride/diglyceride lipase from monoglyceride lipase of chicken adipose tissue.
L. Berglund (1980)
Anandamide Amidohydrolase Activity in Rat Brain Microsomes
F. Desarnaud (1995)
Cannabinoid receptor genes
E. Onaivi (1996)
Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue.
H. Tornqvist (1976)

This paper is referenced by
A spectrophotometric assay for fatty acid amide hydrolase suitable for high-throughput screening.
P. D. De Bank (2005)
Endocannabinoids: synthesis and degradation.
V. Di Marzo (2006)
Novel selective and metabolically stable inhibitors of anandamide cellular uptake.
G. Ortar (2003)
Effets motivationnels de la nicotine chez le rat. Implication des endocannabinoïdes et d'autres systèmes de neurotransmission.
B. Forget (2007)
Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors.
R. Pertwee (1999)
The life cycle of the endocannabinoids: formation and inactivation.
S. Alexander (2009)
Studies on OX1 Orexin Receptor Coupling to Arachidonic Acid and Endocannabinoid Signaling
Pauli M Turunen (2012)
Novel Physiologic Functions of Endocannabinoids as Revealed Through the Use of Mutant Mice
G. Kunos (2004)
Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors
S. Holt (2005)
Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH.
Leonie Wyffels (2009)
Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer.
Daniel K. Nomura (2011)
Monoglyceride Lipase as an Enzyme Hydrolyzing 2‐Arachidonoylglycerol
S. Saario (2007)
Fatty acid amide hydrolase - A target for anti-inflammatory therapies?
S. Holt (2005)
A hydrolase enzyme inactivating endogenous ligands for cannabinoid receptors.
N. Ueda (1998)
Quick Anandamide transport
M. J. McFarland (2004)
Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase.
T. Bisogno (1998)
Therapeutic Potential of Cannabinoids in CNS Disease
J. Croxford (2003)
Endogenous cannabinoids in neuronal and immune cells: toxic effects, levels and degradation.
M. Maccarrone (2001)
Modulators of endocannabinoid enzymic hydrolysis and membrane transport.
W. Ho (2005)
Immunolocalization of cannabinoid receptor 1 (CB1), monoglyceride lipase (MGL) and fatty-acid amide hydrolase 1 (FAAH) in the pig claustrum
A. Pirone (2020)
An investigation into the pharmacological effects of phytocannabinoids and endocannabinoids in human mesenteric arteries
Christopher P. Stanley (2013)
Progesterone reverts LPS-reduced FAAH activity in murine peripheral blood mononuclear cells by a receptor-mediated fashion
M. Wolfson (2013)
Anandamide amidohydrolase (fatty acid amide hydrolase).
N. Ueda (2000)
Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells.
S. Zimov (2007)
Investigation of Endocannabinoid System Signalling Pathways and Their Regulations in Endometrial Carcinoma
T. Ayakannu (2017)
Neuroprotection: Glutamate and Endocannabinoids
H. Hansen (2005)
Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid.
K. Laine (2002)
Glucocorticoid-regulated crosstalk between arachidonic acid and endocannabinoid biochemical pathways coordinates cognitive-, neuroimmune-, and energy homeostasis-related adaptations to stress.
Renato Malcher-Lopes (2009)
Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty acid amides.
M. Patricelli (2001)
The endogenous cannabinoid system and the treatment of marijuana dependence
D. Piomelli (2004)
Removal of Endocannabinoids by the Body: Mechanisms and Therapeutic Possibilities
C. Fowler (2008)
Perspectives in Pharmacology Mechanisms of Endocannabinoid Inactivation : Biochemistry and Pharmacology
Andrea Giuffrida (2017)
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