Click here for the function of FAAH.
Edit this page in Wiki Genes - FAAH or see Wiki Gene.
They are rapidly degraded by the fatty acid amide hydrolase ( FAAH). Paper-12599966.
We tested the impact on DSI duration by blockers of FAAH, COX-2, MGL and ABHD6. Paper-13935267.
JNJ-1661010 is >100-fold preferentially selective for FAAH-1 when compared to FAAH-2. Paper-13550535.
Thus, the enzyme of CMK cells is distinguishable from anandamide amidohydrolase. Paper-1948608.
FAAH mRNA expression correlated with IL-8 mRNA expression in CD lesions (r = 0.53). Paper-13521859.
Deletion of a proline-rich region and a transmembrane domain in fatty acid amide hydrolase. Paper-1929427.
Variants in the CNR1 and the FAAH Genes and Adiposity Traits in the Community. Paper-13684940.
Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolase. Paper-8960981.
The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase ( FAAH). Paper-12695315.
We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry. Paper-10190977.
We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry. Paper-10025744.
Again, 5, 6, and 7 were tested against CB1, CB2, and FAAH without significant activity. Paper-13516784.
Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. Paper-11127302.
Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase ( FAAH) in the human placenta. Paper-10190977.
Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase ( FAAH) in the human placenta. Paper-10025744.
Effects of a short-term exposure to alcohol in rats on FAAH enzyme and CB1 receptor in different brain areas. Paper-13492028.
These results indicate the involvement of both MAGL and FAAH on 2-acylglycerol hydrolysis. Paper-14037478.
Analysis of the FAAH promoter showed a cAMP-response element-like site, which is a transcriptional target of STAT3. Paper-9717593.
A series of para-substituted phenolic N-alkyl carbamates were evaluated for their FAAH and MGL inhibitory activities. Paper-13750240.
Synergy between Enzyme Inhibitors of Fatty Acid Amide Hydrolase and Cyclooxygenase in Visceral Nociception. Paper-13693054.
Similarly the chemical synthesis of various ligands in the remaining areas of CB1/ VR1, AMT and FAAH are described. Paper-9595304.
Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase ( FAAH). Paper-11251328.
Fatty acid amide hydrolase ( FAAH) has attracted significant attention due to its promise as an analgesic target. Paper-14013310.
However, the cellular localization of the CB1 cannabinoid receptor and FAAH in the human placenta has not been determined. Paper-10190977.
However, the cellular localization of the CB1 cannabinoid receptor and FAAH in the human placenta has not been determined. Paper-10025744.
Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). Paper-11127302.
Our data suggest that both COX2 and FAAH play a role in the metabolism of endocannabinoids and related molecules. Paper-12865821.
(2S,9Z)-Octadec-9-ene-1,2-diamine selectively inhibits MGL (K(i) 21.8 microM) without significantly affecting FAAH. Paper-13042987.
The results indicate that URB597, while potent at inhibiting FAAH, does not affect TGH and TGL activities in rat tissues. Paper-12277203.
Fatty acid amide hydrolase ( FAAH) is a pharmaceutical target whose inhibition may lead to valuable therapeutics. Paper-13144015.
RESULTS: URB597 (.3 mg/kg, intravenous) blocked FAAH activity and increased anandamide levels throughout the monkey brain. Paper-13089880.
NAAA reveals no sequence homology with FAAH and belongs to the choloylglycine hydrolase family. Paper-13405828.
The Fatty Acid Amide Hydrolase ( FAAH) Pro129Thr Polymorphism is not Associated with Severe Obesity in Greek Subjects. Paper-13093649.
This MiniReview summarizes the literature concerning the potential therapeutic potential of FAAH and MGL inhibitors. Paper-12513838.
Identification of productive inhibitor binding orientation in fatty acid amide hydrolase ( FAAH) by QM/MM mechanistic modelling. Paper-12664576.
In rat brain homogenate, the reversed amides possessed significantly higher stability against FAAH induced degradation than AEA. Paper-12043787.
Inhibition of fatty acid amide hydrolase produces PPAR-alpha-mediated analgesia in a rat model of inflammatory pain. Paper-13484075.
Glial expression of cannabinoid CB(2) receptors and fatty acid amide hydrolase are beta amyloid-linked events in Down's syndrome. Paper-12689551.
Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 ( CNR1) and fatty acid amide hydrolase ( FAAH) genes. Paper-13012476.
The immunosignals for the CB2 receptor, NAPE-PLD, and FAAH found in pinealocytes did not vary under a 12 hr light:12 hr dark cycle. Paper-13078515.
BACKGROUND: Fatty acid amide hydrolase ( FAAH) and monoglyceride lipase ( MGLL) are the major endocannabinoid metabolic enzymes. Paper-13332730.
The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. Paper-13622600.
The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases. Paper-12154362.
Fatty acid amide hydrolase ( FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors. Paper-13743637.
Fatty acid amide hydrolase ( FAAH) is the oldest and the best characterised enzyme involved in the degradation of endocannabinoids. Paper-11539165.
Here we employed activity-based protein profiling ( ABPP) to assess the selectivity of FAAH inhibitors in multiple rat and human tissues. Paper-13139248.
Compound 9c (1-(4'-pentenoyl-3-(4'-pentenyl)-2-azetidinone)) featured an IC(50) value of 4.5 microM and a good selectivity for FAAH versus MGL. Paper-13082571.
Here we present evidence that the FAAH inhibitor, URB, interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus. Paper-13687201.
These results suggested that NAAA and FAAH cooperatively degraded various N-acylethanolamines in macrophages. Paper-11280028.
The data demonstrate that the ECS is activated in obese visceral adipose tissue as shown by decreased FAAH, Cb1, and adiponectin expression. Paper-13400243.
Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors. Paper-13158757.
Consistently, inhibitors of 5-lipoxygenase, but not those of cyclooxygenase, significantly counteracted the inhibition of FAAH by AEA or 2-AG. Paper-8613741.
AEA is metabolized by fatty acid amidohydrolase ( FAAH) and 2-AG is metabolized by both FAAH and monoacylglycerol lipase ( MAGL). Paper-13143957.
Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. Paper-13134528.
OBJECTIVE: To determine whether the single nucleodtide polymorphisms of the FAAH and MGLL genes are associated with alcoholism in a Japanese population. Paper-13332730.
AEA synthesized by multiple pathways, including NAPE-specific phospholipase D ( NAPE-PLD) and degraded by the fatty acid amide hydrolase ( FAAH). Paper-13812169.
An additional endogenous substance with REM sleep-inducing properties, 2-octyl gamma-bromoacetoacetate, was characterized as a potent FAAH inhibitor. Paper-1821209.
Specifically, NPs produce endocannabinoids and express the CB1 receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase ( FAAH). Paper-10979053.
2-AG is preferentially degraded by monoacylglycerol lipase ( MGL), whereas anandamide is hydrolyzed primarily by fatty-acid amide hydrolase ( FAAH). Paper-11343225.
Linking FAAH, VR1, and anandamide implies a coupling among the remaining "older" parts of the endocannabinoid system, MGL, CB receptors, and 2-AG. Paper-10268689.
The genotype distribution indicates there is a relationship between the TaqIA SNP, CNR1 and FAAH genes and PCL-R's Factor 1 in alcoholic patients. Paper-13197426.
CB1 and CB2 receptors and FAAH densities and cellular sites of expression were examined using immunohistochemistry and immunofluorescence. Paper-13134528.
Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. Paper-10162428.
Following CMS, CB1 receptor and fatty-acid-amide-hydrolase ( FAAH) expression levels in the hippocampus were assessed by western blot analysis. Paper-13882959.
In PC-3 cells, overexpression of FAAH resulted in increased FAAH protein, 2-AG hydrolysis, cell invasion and cell migration. Paper-12888190.
CONCLUSIONS: In the monkey brain, the FAAH inhibitor URB597 increases anandamide levels while causing a compensatory down-regulation in 2-AG levels. Paper-13089880.
The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Paper-11127302.
Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase ( FAAH) enzyme. Paper-13213492.
Structure-property relationships of a class of carbamate-based fatty acid amide hydrolase ( FAAH) inhibitors: chemical and biological stability. Paper-13964364.
The aim of this study was to examine the role of fatty acid amide hydrolase ( FAAH) on ethanol sensitivity, preference, and dependence. Paper-12678361.
In addition, the ability of the compounds to inhibit the hydrolysis of anandamide by fatty acid amide hydrolase ( FAAH) was investigated. Paper-11269465.
Cyclohexylcarbamic acid aryl esters are a class of fatty acid amide hydrolase ( FAAH) inhibitors, which includes the reference compound URB597. Paper-13964364.
Conversely, small-interfering RNA (siRNA) knockdown of FAAH in LNCaP cells decreased FAAH protein, 2-AG hydrolysis and cell invasion. Paper-12888190.
Fatty acid amide hydrolase contains a proline-rich sequence matching a consensus sequence for SH3-binding domains as well as a transmembrane domain. Paper-1929427.
Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. Paper-9364875.
One such agent, the fatty-acid amide hydrolase ( FAAH) inhibitor URB597, selectively increases anandamide levels in the brain of rodents and primates. Paper-13531496.
Additionally, SDS-PAGE analysis of the recombinant proteins identified the presence of SDS-resistant oligomers for WT- FAAH, but not for DeltaTM- FAAH. Paper-1616520.
NAAA mRNA as well as FAAH mRNA was detected in several macrophage-like cells, including RAW264.7, and mouse peritoneal macrophages. Paper-11280028.
Association study between alcoholism and endocannabinoid metabolic enzyme genes encoding fatty acid amide hydrolase and monoglyceride lipase in a Japanese population. Paper-13332730.
Modulation of the anti-nociceptive effects of 2-arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model. Paper-13087783.
Activity-based protein profiling ( ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Paper-13747934.
The compounds were generally selective for FAAH, with IC(50) values in the nM range, whereas inhibition of MGL required concentrations three orders of magnitude higher. Paper-13750240.
The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase ( FAAH) inhibition. Paper-12674526.
This SPA uses the specific interactions of [3H]R(+)-methanandamide ( MAEA) and FAAH expressing microsomes to evaluate the displacement activity of FAAH inhibitors. Paper-12120351.
Clinical remission was accompanied by a significant decrease of the levels of anandamide (3.88 +/- 0.72 pmol/ml) and of the mRNA transcripts for CB2 receptors and FAAH. Paper-10670103.
We investigated the status of cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase ( FAAH) enzyme in brain tissue samples obtained from MS patients. Paper-13134528.
The action of anandamide (AEA) can be prolonged by inhibiting its degradation, through the use of URB597 ( URB), a Fatty Acid Amide Hydrolase ( FAAH) enzyme inhibitor. Paper-13687201.
The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN). Paper-13503288.
Western blot and immunocytochemistry analyses of RBL-2H3 cells revealed that FAAH was localized in intracellular compartments distinct from caveolin-1 localization. Paper-10614952.
Analysis of the FAAH promoter showed an Ikaros binding site, and mutation of this site prevented FAAH activation by progesterone in transient expression assays. Paper-9965375.
In this study, we examined the distribution of the cannabinoid receptors, CB1 and CB2, and the endocannabinoid-metabolizing enzyme FAAH in first trimester human placenta. Paper-10864222.
Transcripts for CB1, CB2, and FAAH were demonstrated in first trimester trophoblast extracts with only the CB1 transcript being significantly regulated. Paper-13007847.
A variety of long chain 1,2-diamines and related compounds were synthesized and tested for their activity on fatty acid amide hydrolase ( FAAH) and monoacyglycerol lipase ( MGL). Paper-13042987.
The basal SCAAT gene expression pattern revealed an upregulation of the FAAH in the OB (p=0.03 vs L), whereas similar CB-1 and CB-2 mRNA levels were seen. Paper-12519860.
Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase ( FAAH) and monoacylglycerol lipase ( MAGL). Paper-13953642.
These results suggest that FAAH regulates 2-AG hydrolysis and invasion of prostate carcinoma cells and is potentially involved in prostate tumorigenesis. Paper-12888190.
It has been clearly demonstrated that 2-AG degradation is mainly catalysed not only by monoacylglycerol lipase ( MGL) but also by a fatty acid amide hydrolase ( FAAH). Paper-13087783.
Effects of inhibition of fatty acid amide hydrolase vs. the anandamide membrane transporter on TRPV1-mediated calcium responses in adult DRG neurons; the role of CB receptors. Paper-12415840.
Association in alcoholic patients between psychopathic traits and the additive effect of allelic forms of the CNR1 and FAAH endocannabinoid genes, and the 3' region of the DRD2 gene. Paper-13197426.
CONCLUSIONS AND IMPLICATIONS: Possibly due to its dual activity as a FAAH inhibitor and TRPV1 antagonist, AA-5-HT was highly effective against both acute and chronic peripheral pain. Paper-13158757.
Immunoreactivity for CB1, NAPE-PLD, and FAAH was localized in the postacrosomal region and in the midpiece, whereas for TRPV1, it was restricted to the postacrosomal region. Paper-14004484.
AM404 inhibits endocannabinoid cellular uptake, binds weakly to CB1 and CB2 cannabinoid receptors, and is formed by fatty acid amide hydrolase ( FAAH) in vivo. Paper-13516784.
In addition, it indicates an increased activation of CB1 receptors as a mechanism underlying the effects of FAAH inhibition in two models of anxiety. Paper-12674520.
Inhibition of FAAH activity has been suggested as a therapeutic approach for the treatment of chronic pain, depression and anxiety, through local activation of the cannabinoid receptor CB1. Paper-13149278.
Anandamide administration alone and after inhibition of fatty acid amide hydrolase ( FAAH) increases dopamine levels in the nucleus accumbens shell in rats. Paper-12052619.
Internalized AEA was hydrolyzed by a fatty acid amide hydrolase ( FAAH), whose activity became measurable only in the presence of 5-lipoxygenase, but not cyclooxygenase, inhibitors. Paper-2149108.
CONCLUSIONS AND IMPLICATIONS: Cannabidiol selectively reduces croton oil-induced hypermotility in mice in vivo and this effect involves cannabinoid CB1 receptors and FAAH. Paper-12860743.
Co-expression of TRPV1, CB1/ CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Paper-13524376.
For the FAAH and the membrane- bound MAGL, there was no obvious relationship between the degree of unsaturation of the acyl side chain and the ability to inhibit the enzymes. Paper-11269465.
Furthermore, HeLa cells, which do not express high levels of FAAH, showed an accumulation of tritium in the caveolin-rich membrane fraction only when transfected with FAAH cDNA. Paper-10614952.
To study this process, AEA uptake and hydrolysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondria, or the Golgi apparatus. Paper-13719679.
There was no difference in the myocardial cannabinoid CB(1) and CB(2) receptor gene expression between young and aging FAAH(-/-) and FAAH(+/+) mice. Paper-13368993.
Progesterone activates fatty acid amide hydrolase ( FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin. Paper-9965375.
Fatty acid amide hydrolase ( FAAH) is an integral membrane enzyme that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide. Paper-12540254.
In conclusion, the endocannabinoid 2-AG, as well as other 2-acylglycerols, are substrates of both FAAH and MAGL; the latter was characterized for the first time in platelets. Paper-14037478.
Further study in European American subjects found significant associations between short duration cold pain sensitivity and variations in TRPA1, COMT, and FAAH in a gender dependent manner. Paper-12161367.
CONCLUSIONS: Endocannabinoids engage functional CB(1) receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Paper-12998832.
The endocannabinoid system consists of two cannabinoid (CB) receptors, seven ligands, and ligand-catabolizing enzymes such as fatty acid amid hydrolase ( FAAH) and monoglyceride lipase ( MGL). Paper-10268689.
In contrast, the anandamide hydrolysis in mouse brain appeared to be principally attributable to FAAH despite the expression of NAAA in the brain. Paper-11280028.
A study of the structure-activity relationships (SAR) of 2f ( OL-135), a potent inhibitor of fatty acid amide hydrolase ( FAAH), is detailed, targeting the 5-position of the oxazole. Paper-13140158.
The impact of cannabinoid CB(1) receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test, and models of unconditioned and conditioned social defeat. Paper-12998832.
Taken together, these results suggest that leptin, by up-regulating the FAAH promoter through STAT3, enhances FAAH expression, thus tuning the immunomodulatory effects of anandamide. Paper-9717593.
In a search for novel TRPA1 agonists, we identified 3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate ( URB597), a potent and systemically active inhibitor of fatty acid amide hydrolase ( FAAH). Paper-13204288.
A naturally occurring missense polymorphism in the gene encoding fatty acid amide hydrolase ( FAAH), the primary enzyme for inactivation of endocannabinoids, is associated with problem drug use. Paper-11251328.
Unlike NADA, OLDA was only a weak ligand for rat CB1 receptors; but like NADA, it was recognized by the anandamide membrane transporter while being a poor substrate for fatty-acid amide hydrolase. Paper-9668679.
The analgesic effect of N-arachidonoyl-serotonin, a FAAH inhibitor and TRPV1 receptor antagonist, associated with changes in rostral ventromedial medulla and locus coeruleus cell activity in rats. Paper-13057563.
The activation of FAAH by progesterone was paralleled by a decrease (down to 60%) of the cellular levels of anandamide and involved increased nuclear levels of the transcription factor Ikaros. Paper-9965375.
In vitro, KDS-4103 inhibits FAAH activity with median inhibitory concentrations (IC(50)) of 5 nM in rat brain membranes and 3 nM in human liver microsomes. Paper-12062804.
These findings demonstrate novel mechanisms for memory enhancement by activation of PPAR-alpha, either directly by administering a PPAR-alpha agonist or indirectly by administering a FAAH inhibitor. Paper-13743637.
PC-NAEs were very poor substrates for FAAH; however, a vanadate-sensitive enzymatic activity was detected in brain membranes that converted PC-NAEs back to their parent NAEs. Paper-12233942.
Moreover, we found that AM404 specifically inhibited both IL-2 and TNF-alpha gene transcription and TNF-alpha synthesis in CD3/ CD28- stimulated Jurkat T cells in a FAAH independent way. Paper-13132894.
These data coupled with the overlapping, but distinct tissue distributions of FAAH-1 and FAAH-2 suggest that these proteins may collaborate to control fatty acid amide catabolism in primates. Paper-12332160.
Fatty acid amide hydrolase ( FAAH), a membrane-anchored enzyme responsible for the termination of endocannabinoid signalling, is an attractive target for treating conditions such as pain and anxiety. Paper-12685610.
This effect was not associated with covalent modifications of FAAH, since specific inhibitors of farnesyltransferase, kinases, phosphatases, glycosyltransferase or nitric oxide synthase were ineffective. Paper-8613741.
Our observations demonstrate that genetic variations in TRPA1, COMT, and FAAH contribute gender specifically to individual variations in short duration cold pain sensitivity in a European American cohort. Paper-12161367.
The structure-activity relationships (SAR) of alkylcarbamic acid aryl esters and the discovery of potent archidonylsulfonyl derivatives as fatty acid amide hydrolase ( FAAH) inhibitors are summarized. Paper-11171640.
Here we present immunohistochemical evidence that both CB(2) receptors and FAAH enzyme are induced in Abeta plaque-associated microglia and astroglia, respectively, in Down's syndrome. Paper-12689551.
Self-association through FAAH's transmembrane domain was further demonstrated by a FAAH transmembrane domain-GST fusion protein which formed SDS-resistant dimers and large oligomeric assemblies in solution. Paper-1616520.
A membrane bound amidohydrolase ( fatty acid amide hydrolase, FAAH), located intracellulary, hydrolyzes and inactivates anandamide and other endogenous cannabinoids such as 2-arachidonoylglycerol (2-AG). Paper-8579671.
The enzymes, fatty acid amide hydrolase ( FAAH) and N-acyclphosphatidylethanolamine-phospholipase D ( NAPE-PLD), were only found in growing secondary and tertiary follicles and corpora lutea and albicantes. Paper-13629581.
This study was aimed at finding structural requirements for the interaction of the acyl chain of endocannabinoids with cannabinoid receptors, membrane transporter protein, and fatty acid amide hydrolase ( FAAH). Paper-9530181.
Spinal inhibition of FAAH, with either URB597 or arachidonoyl serotonin (AA-5-HT), also enhanced SIA through a CB1-mediated mechanism, presumably by increasing accumulation of tonically released anandamide. Paper-11343225.
Both AEA-binding receptors ( CB1 and TRPV1) exhibited a functional binding activity; enzymatic activity was demonstrated for NAPE-PLD, FAAH, and the purported endocannabinoid membrane transporter (EMT). Paper-14004484.
FAAH's emergence correlates with VR1's newly-found affinity for anandamide; this overlap in evolutionary time is recapitulated by complementary distribution patterns of FAAH, VR1, and anandamide in the brain. Paper-10268689.
Here, we tested the hypothesis that temporal-spatial expression of FAAH, CB1, and CB2 is regulated during early pregnancy and that anandamide detrimentally alters trophoblast proliferation. Paper-13007847.
The biological targets for endocannabinoids include the cannabinoid receptors ( CB1 and CB2), the enzyme anandamide amidohydrolase ( AAH), and the carrier protein referred to as the anandamide transporter (ANT). Paper-8432326.
We have studied the status of some of the components of the endocannabinoid system, fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with Alzheimer's disease. Paper-10162428.
The level of 2-arachidonoyl-glycerol was unchanged as was the activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolyzing phospholipase D, and fatty acid amide hydrolase upon starvation and re-feeding. Paper-11806091.
More generally, the studies revealed 12 selective in vitro inhibitors for FAAH (mostly octylsulfonyl and octylphosphonyl derivatives) and 9 for NTE (mostly benzodioxaphosphorin oxides and organophosphorus fluoridates). Paper-9397981.
These data indicate that inhibition of FAAH and MAGL reduces neuropathic pain through distinct receptor mechanisms of action and present viable targets for the development of analgesic therapeutics. Paper-13944391.
In fact, lymphocyte treatment with IL-4 or with IL-10 had a stimulating effect on FAAH, whereas the Th1 cytokines IL-12 and IFN-gamma reduced the activity and the protein expression of FAAH. Paper-8843744.
A novel fluorescent assay to continuously monitor fatty acid amide hydrolase ( FAAH) activity that is simple, sensitive, and amenable to high-throughput screening (HTS) of compound libraries is described in this article. Paper-10740061.
The bilayer location for 1 revealed by these studies may be important for the interaction of 1 with membrane-embedded proteins such as the cannabinoid CB1 receptor and membrane- associated proteins such as FAAH. Paper-11136087.
Moreover, an enzyme that inactivates endocannabinoids, fatty acid amide hydrolase, appears to be preferentially targeted to the somatodendritic compartment of neurons that are postsynaptic to CB1-expressing axon terminals. Paper-8794707.
In vitro, paraoxon inhibited hippocampal cholinesterase and fatty acid amide hydrolase activities, and displaced specific binding to the cannabinoid receptor ligand ([(3)H]CP 55,940) in a concentration-dependent manner. Paper-12244098.
The effect of AA-5-HT was mimicked by co-injecting the selective FAAH inhibitor URB597 and the selective TRPV1 antagonist I-RTX into the PAG, which also induced analgesia and inhibition of ON and OFF cell ongoing activities. Paper-13057563.
Together, these data suggest that following uptake via caveola/lipid raft-related endocytosis, anandamide is rapidly metabolized by FAAH, with the metabolites efficiently recycled to caveolin-rich membrane domains. Paper-10614952.
Fatty acid amide hydrolase ( FAAH) is a serine hydrolase responsible for the degradation of anandamide, an endogenous cannabinoid agonist, and oleamide, a sleep-inducing lipid. Paper-11178942.
Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase ( FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. Paper-13368993.
The recent availability of the X-ray structures of Pam, fatty acid amide hydrolase, and malonamidase E2 has led to the proposal of a novel Ser-Ser-Lys catalytic triad mechanism for the amide hydrolysis by the AS enzymes. Paper-10938540.
In this article, we review evidence suggesting that (i) cannabis influences brain endocannabinoid signaling and (ii) FAAH inhibitors such as URB597 might offer a possible therapeutic avenue for the treatment of cannabis withdrawal. Paper-13531496.
Furthermore, the inhibition of FAAH causes an accumulation of AEA but not 2-AG, which, being 200-fold more abundant than AEA in the brain, might differently modulate CB(1)-mediated behavioral responses. Paper-13892877.
These endogenous neuromodulators involved in the cannabinergic system are thought to be produced on demand and are metabolized by the enzymes fatty acid amide hydrolase ( FAAH) and monoacylglycerol lipase ( MAG lipase). Paper-9595303.
We report the discovery of a novel, chiral azetidine urea inhibitor of Fatty Acid Amide Hydrolase ( FAAH,) and describe the surprising species selectivity of VER-156084 versus rat and human FAAH and also hCB1. Paper-13885282.
The former and latter bands were very faint and were also detected in whole homogenates from the coelenterate Hydra vulgaris, where the presence of CB1-like receptors, endocannabinoids and a FAAH-like activity was reported previously. Paper-8821107.
Using a passive-avoidance task in rats, we found that memory acquisition was enhanced by the FAAH inhibitor URB597 or by the PPAR-alpha agonist WY14643, and these enhancements were blocked by the PPAR-alpha antagonist MK886. Paper-13743637.
The homogenates of RAW264.7 cells showed both the NAAA and FAAH activities which were confirmed with the aid of their respective specific inhibitors, N-cyclohexanecarbonylpentadecylamine (CCP) and URB597. Paper-11280028.
Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase ( FAAH) is mediated by CB1 receptors. Paper-12674520.
Two endocannabinoid deactivating enzymes, fatty acid amide hydrolase ( FAAH) and soluble monoacylglycerol lipase ( MGL), are increasingly prominent targets for inhibitors that indirectly potentiate endocannabinoid-system signalling. Paper-13717463.
We investigated if AA-5-HT antagonizes the transient receptor potential vanilloid-1 ( TRPV1) channel and, as FAAH and TRPV1 are targets for analgesic compounds, if it exerts analgesia in rodent models of hyperalgesia. Paper-13158757.
Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration--comparison with CB(1) receptor blockade. Paper-13904848.
We prepared three derivatives of this new (endo)cannabinoid using bioisosteric replacement (1), homology (2), and derivatization (3) of the 4-aminophenol moiety in AM404 and tested them against CB1, CB2, and FAAH. Paper-13516784.
The CNR1 SNP displayed a significant abstinence x genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence x genotype interaction on craving. Paper-13012476.
Currently, three enzymes have been characterized with the ability to hydrolyze endocannabinoids: fatty acid amide hydrolase ( FAAH), monoglyceride lipase ( MGL) and N-acylethanolamine-hydrolyzing acid amidase ( NAAA). Paper-11154225.
In the presence of the specific fatty acid amide hydrolase ( FAAH) inhibitors URB597 and AM374, though, 2-OG hydrolysis was inhibited up to 55% in a concentration-dependent manner (IC(50) = 129.8 nM and 20.9 nM respectively). Paper-14037478.
We hypothesize that common genetic variants in the CNR1 ( encoding endocannabinoid receptor 1) and FAAH genes (encoding fatty acid amide hydrolase, a key enzyme hydrolyzing endocannabinoids) are associated with adiposity traits. Paper-13684940.
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. Paper-12865821.
PF-3845 selectively inhibits FAAH in vivo, as determined by activity-based protein profiling; raises brain anandamide levels for up to 24 hr; and produces significant cannabinoid receptor-dependent reductions in inflammatory pain. Paper-13732154.
To address this question we compared the effects of local inhibition of FAAH versus COX2 (URB597 and nimesulide, respectively) on inflammatory hyperalgesia and levels of endocannabinoids and related molecules in the hindpaw. Paper-12865821.
CONCLUSION: As we found no evidence for an association of genetic variation in CNR1, FAAH, NAAA and MGLL with AN, we conclude that genetic variations in these genes do not play a major role in the etiology of AN in our study groups. Paper-13503288.
(ii) Degradation by fatty acid amide hydrolase limits anandamide activity on VR1; and (iii) the anandamide membrane transporter inhibitors can be used to distinguish between CB(1) or VR1 receptor-mediated actions of anandamide. Paper-8800861.
9. Interestingly, mutation of each of FAAH's conserved histidines (H184, H358, and H449) generated active enzymes, indicating that FAAH does not contain a Ser-His-Asp catalytic triad commonly found in other mammalian serine hydrolytic enzymes. Paper-1958187.
Furthermore, as it is known that anandamide can bind several other targets than CB1 receptors, we investigated whether FAAH inhibition reduces anxiety via CB1 receptors. Paper-12674520.
Two single nucleotide polymorphisms ( SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers. Paper-13012476.
Peripheral administration of endocannabinoids or MGL/ FAAH inhibitors is a promising analgesic approach requiring further investigation.British Journal of Pharmacology (2008) 155, 913-924; doi:10.1038/bjp.2008.322; published online 11 August 2008. Paper-13087783.
Thus a meta-analysis of ligand extraction studies was performed (chemotaxonomy), and compared to a molecular search for homologs of CB receptors, vanilloid receptors ( VR1), FAAH, and MGL in the genomes of sequenced organisms (phylogenomics). Paper-10268689.
Finally, the FAAH gene expression positively correlated with the fasting serum insulin concentration (r 0.66; p=0.01), whereas an inverse association with the whole-body glucose disposal (r -0.58; p<0.05) was seen. Paper-12519860.
AIM: To examine whether withdrawal after abstinence and cue-elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 ( CNR1) and fatty acid amide hydrolase ( FAAH). Paper-13012476.
After correction for multiple testing, none of the SNPs in the CNR1 gene or in the FAAH gene displayed statistical evidence for association with BMI, waist circumference, and visceral adipose tissue or subcutaneous adipose tissue (all P > 0.18). Paper-13684940.
In particular, it has been shown that pharmacological inhibition of the enzyme fatty acid amide hydrolase ( FAAH), which catalyzes the intracellular hydrolysis of anandamide, elicits anxiolytic-like and antidepressant-like effects in rodents. Paper-12594736.
As seen for other neuroinflammatory conditions, selective glial expression of cannabinoid CB1 and CB2 receptors and FAAH enzyme is induced in MS, thus supporting a role for the endocannabinoid system in the pathogenesis and/or evolution of this disease. Paper-13134528.
Fatty acid amide hydrolase ( FAAH) and monoglyceride lipase ( MGL) are the main enzymes responsible for the hydrolysis of endogenous cannabinoids N-arachidonoylethanolamide ( AEA) and 2-arachidonoylglycerol ( 2-AG), respectively. Paper-13908605.
Several organophosphorus pesticides and related compounds are shown in this study to be more potent in vivo inhibitors of mouse brain FAAH than neuropathy target esterase ( NTE), raising the question of the potential toxicological relevance of FAAH inhibition. Paper-9397981.
Protein expression was revealed for CB1 ( approximately 56 kDa), TRPV1 ( approximately 95 kDa), AEA-synthesizing phospholipase D (NAPE-PLD) ( approximately 46 kDa), and AEA-hydrolyzing enzyme [ fatty acid amide hydrolase ( FAAH), approximately 66 kDa]. Paper-14004484.
The characterization, cloning, and neuronal distribution of FAAH have been detailed and the enzyme was found to possess the ability to hydrolyze a range of fatty acid amides including anandamide which serves as the endogenous ligand for the cannabinoid receptor. Paper-1821209.
Adverse effects of elevated levels of anandamide on these processes resulting from FAAH inactivation are mimicked by administration of (-)-Delta9-tetrahydrocannabinol (THC; the major psychoactive constituent of marijuana), due to enhanced signaling via CB1. Paper-12078770.
In this study we describe the presence of not only CB1, but also CB2, TRPV1 and the degrading enzyme FAAH in human and rodent skeletal muscle using reverse transcription polymerase chain reaction ( RT-PCR). Paper-12532849.
We show that, unlike CB1R and PLD, the activity of AMT and the activity and expression of FAAH increase while the endogenous levels of AEA decrease in HaCaT and NHEK cells induced to differentiate in vitro by 12-O-tetradecanoylphorbol 13-acetate (TPA) plus calcium. Paper-9977898.
The X-ray crystal structures of five distinct enzymes ( prostaglandin H(2) synthase, squalene cyclase, fatty acid amide hydrolase, microsomal cytochrome P450, and estrone sulfatase) challenge contemporary descriptions of integral membrane proteins. Paper-10308079.
We have also shown that progesterone, alone or additively with leptin, up-regulates the FAAH gene in human T-cells, through the Ikaros transcription factor [Maccarrone, M., Bari, M., Di Rienzo, M., Finazzi-Agro, A., & Rossi, A. (2003) J. Biol. Chem. 278, 32726-32732]. Paper-10853319.
Fatty acid amide hydrolase ( FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Paper-11021830.
The selected SNPs captured 85% (r(2) = 0.8) of the common variation (minor allele frequency >5%) at the CNR1 locus and 96% (r(2) = 0.8) of the common variation at the FAAH locus (defined as the genomic segment containing the gene +20 kb upstream and +10 kb downstream). Paper-13684940.
In support of this, we observed kinetics consistent with rate-limited diffusion at 0 degrees C. Novel transport inhibitors have been synthesized that are either weak FAAH inhibitors or do not inhibit FAAH in vitro (e.g. UCM707, OMDM2, and AM1172). Paper-11310213.
In normal rats, the TRPV1 agonist capsaicin (1mg/kg) or the FAAH inhibitor URB597 (10mg/kg) caused a significant reduction in movement in both the horizontal (locomotion) and vertical (rearing) planes (-45% and -53% respectively with capsaicin; -33% and -37% for URB597). Paper-12183064.
As systemic administration of TRPV1 ligands reduces locomotor activity in normal rodents, we hypothesised that activation of TRPV1 by endocannabinoids could play a role in the control of voluntary movement and that such actions could be regulated by AMT and FAAH. Paper-12183064.
In this study, a series of unbranched p-nitroanilide (pNA) substrates ranging from 6 to 20 carbons in length was used to probe the acyl chain binding specificity of FAAH, revealing that this enzyme exhibits a strong preference for acyl chains 9 carbons in length or longer. Paper-8960981.
We also show that estrogen binding to surface receptors leads to stimulation of the anandamide-synthesizing enzyme phospholipase D and to inhibition of the anandamide-hydrolyzing enzyme fatty acid amide hydrolase, the latter effect mediated by 15-lipoxygenase activity. Paper-9276046.
Several enzymes have been proposed to play a role in 2-AG breakdown, presumably determining the time course of DSI: fatty acid amide hydrolase ( FAAH), cyclooxygenase-2 ( COX-2), monoacyl glycerol lipase (MGL), and alpha/beta-hydrolase domains 6 and 12 (ABHD6 and ABHD12). Paper-13935267.
In particular, other elements of the ECS, such as the fatty acid amide hydrolase ( FAAH) or the CB(2) cannabinoid receptor are now considered as promising pharmacological targets for some diseases and new cannabinoids have been incorporated as therapeutic tools. Paper-12528580.
In addition, the hit molecules from the virtual screening of CB2 receptor ligands (reported previously in Salo et al. J. Med. Chem. 2005, 48, 7166) were also tested in our FAAH assay, and four active compounds (7-10) were found with IC50 values between 0.52 and 22 microM. Paper-12068883.
Ibu-am5 inhibited the binding of [3H]-CP55,940 to rat brain CB1 and human CB2 cannabinoid receptors more potently than ibuprofen, but the increase in potency was less than the corresponding increase in potency seen for inhibition of FAAH activity. Paper-13259774.
The purpose of this review is to summarize the structure-activity relationships (SAR) of anandamide for the CB1 cannabinoid receptor and to define the structural requirements for the substrates and the inhibitors of anandamide amidohydrolase and the anandamide transporter. Paper-1962761.
The synthetic pathway probably involves synthesis of oleoylglycine and then conversion to oleamide by peptidylglycine alpha-amidating monooxygenase ( PAM); breakdown of oleamide is by fatty acid amide hydrolase ( FAAH). Paper-13188969.
FAAH-compromised animals reliably display antinociceptive and anti-inflammatory phenotypes with a similar efficacy as direct-acting cannabinoid receptor agonists, such as Delta(9)-tetrahydrocannabinol ( THC), the primary psychoactive constituent of Cannabis sativa. Paper-13699803.
The NF-kappaB inhibitory activity of AEA was independent of CB(1) and CB(2) activation in TNFalpha-stimulated 5.1 and A549 cell lines, which do not express vanilloid receptor 1, and was not mediated by hydrolytic products formed through the activity of the enzyme fatty acid amide hydrolase. Paper-9665813.
The aim of this study was to elucidate the acute in vivo effects of insulin on gene expression of the cannabinoid type 1 ( CB-1) and type 2 ( CB-2) receptors, as well as of the fatty acid amide hydrolase ( FAAH) in the sc abdominal adipose tissue (SCAAT). Paper-12519860.
Bioactive N-acylethanolamines, including the endocannabinoid anandamide and anti-inflammatory N-palmitoylethanolamine, are hydrolyzed to fatty acids and ethanolamine in animal tissues by the catalysis of fatty acid amide hydrolase ( FAAH). Paper-13405828.
The genetic analysis involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located nearby the DRD2 gene, the 10-repeat allele of a variable number tandem repeats ( VNTR) of the SLC6A3 gene, the C385A FAAH SNP and the 3'-UTR microsatellite of CNR1 gene. Paper-13197426.
Indeed, long-term treatment of human breast cancer cells (HBCCs) with PEA downregulates the expression of the enzyme responsible for AEA degradation, the fatty acid amide hydrolase, thereby leading to an enhancement of AEA-induced, and cannabinoid CB1 receptor-mediated, cytostatic effect on HBCCs. Paper-9612339.
We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase ( FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Paper-11127302.
The discovery of N-arachidonoylethanolamine ( anandamide, AEA) and of the enzyme that terminates its signaling, i. e. fatty acid amide hydrolase ( FAAH), has inspired pharmacological strategies to augment endocannabinoid tone and biological activity through inhibition of FAAH. Paper-11154254.
The endocannabinoid system consists of endocannabinoids (such as anandamide), their target receptors (mostly cannabinoid CB(1) receptors), and the enzymes that degrade those endocannabinoids ( fatty-acid-amide-hydrolase ( FAAH) for anandamide). Paper-13904848.
The endocannabinoid system consists of two cannabinoid receptors ( CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase ( FAAH) and monoglyceride lipase ( MGL). Paper-12068883.
The most potent compounds, dodecylcarbamic acid 4-(4,5-dihydrothiazol-2-yl)phenyl (12) and 4-(1,2,3-thiadiazol-4-yl)phenyl (26) esters, inhibited FAAH and MGL with IC(50) values at the low-nanomolar (IC(50)s; 0.0063 and 0.012 microM) and the low-micromolar ranges (IC(50)s; 2.1 and 1.0 microM), respectively. Paper-13750240.
Interestingly, human neuroblastoma CHP100 cells also have a leptin receptor (approximately 110 kDa, Kd = 2.2 +/- 0.2 nm, Bmax = 339 +/- 8 fmol.mg protein(-1)), a progesterone receptor (approximately 120 kDa), STAT3 and Ikaros, yet their FAAH is not activated by leptin or progesterone. Paper-10853319.
The search for a highly potent and selective inhibitor for FAAH relative to NTE for use as a toxicological probe culminated in the discovery that octylsulfonyl fluoride inhibits FAAH by 50% at 2 nM in vitro and 0.2 mg/kg in vivo and NTE is at least 100-fold less sensitive in each case. Paper-9397981.
The chemical strategies used for the synthesis of various ligands related to the endocannabinoid system namely anandamide (AEA), 2-arachidonylglycerol ( 2-Ara-Gl), CB1/(vanilloid receptors) VR1, anandamide membrane transporter (AMT) and fatty acid amide hydrolase ( FAAH) are described in this review. Paper-9595304.
Specifically, data obtained in human brain tissue sections from Alzheimer's disease patients showed that the expression of cannabinoid receptors of the CB(2) type is induced in activated microglial cells while fatty acid amide hydrolase ( FAAH) expression is increased in reactive astrocytes. Paper-12689551.
Here we have analyzed human dendritic cells for the presence of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), the cannabinoid CB1 and CB2 receptors, and one of the enzymes mostly responsible for endocannabinoid hydrolysis, the fatty acid amide hydrolase ( FAAH). Paper-9218343.
Furthermore, the enzyme of CMK cells was much less sensitive to phenylmethylsulfonyl fluoride and methyl arachidonoyl fluorophosphonate potently inhibiting anandamide amidohydrolase, and effectively hydrolyzed palmitoylethanolamide, which was a poor substrate for anandamide amidohydrolase. Paper-1948608.
Despite comprehensive SNP mapping across the genes and their regulatory regions in a large unselected sample, we failed to find evidence for an association of common variants in the CNR1 and FAAH genes with measures of adiposity in our community-based sample.Obesity (2009) 17 4, 755-760. doi:10.1038/oby.2008.608. Paper-13684940.
Termination of anandamide signaling by fatty acid amide hydrolase ( FAAH) is well characterized, but less is known about the inactivation of 2-AG, which can be hydrolyzed by multiple enzymes in vitro, including FAAH and monoacylglycerol lipase ( MAGL). Paper-12650765.
The pharmacological modulation of endogenous AA showed that the prevention of AA generation by blockage of cPLA2, diacylglycerol (DAG) lipase and fatty acid hydrolysis ( FAAH), augments hypoxia-induced [Ca(2+)](i) elevation, whereas prevention of AA degeneration attenuates hypoxia-induced [Ca(2+)](i) elevation. Paper-12834514.
Apart from being almost inactive on MAGL, these two compounds showed high selectivity over rat liver triacylglycerol lipase, rat N-acylphosphatidyl-ethanolamine-selective phospholipase D (involved in anandamide biosynthesis), rat fatty acid amide hydrolase and human recombinant cannabinoid CB(1) and CB(2) receptors. Paper-11806085.
These data: (a) provide the first evidence that cisplatin causes a selective increase in 2-AG levels in the brain, and (b) support the established notion that 2-AG may produce some of its effects, including emesis, via downstream metabolites produced independently of FAAH. Paper-11278072.
The synthesis of these endocannabinoids is catalyzed by the N-acylphosphatidylethanolamine-selective phospholipase D ( NAPE-PLD) and the sn-1-selective diacylglycerol lipase (DAGL), whereas their degradation is accomplished by the fatty acid amide hydrolase ( FAAH) and the monoglyceride lipase ( MGL), respectively. Paper-12357522.
The two human FAAH enzymes, which share 20% sequence identity and are referred to hereafter as FAAH-1 and FAAH-2, hydrolyzed primary fatty acid amide substrates (e.g. oleamide) at equivalent rates, whereas FAAH-1 exhibited much greater activity with N-acyl ethanolamines (e.g. anandamide) and N-acyl taurines. Paper-12332160.
For therapeutic purposes, inhibitors of FAAH may provide more specific cannabinoid activities than direct agonists, and several such molecules have already been developed.Pharmacological effects of the endocannabinoids are very similar, yet not identical, to those of the plant-derived and synthetic cannabinoid receptor ligands. Paper-9574493.
The other AEA-binding receptor transient receptor potential channel vanilloid receptor subunit 1, the AEA synthetase N-acyl-phosphatidylethanolamine-phospholipase D, and the AEA hydrolase fatty acid amide hydrolase were not affected by MCD, whereas the AEA membrane transporter was inhibited ( approximately 55%) compared with controls. Paper-12252211.
BACKGROUND AND PURPOSE: Recent studies have demonstrated that the naturally occurring isoflavone compounds genistein and daidzein inhibit the hydrolysis of anandamide by fatty acid amide hydrolase ( FAAH) in the low micromolar concentration range. Paper-12930316.
The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase ( FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. Paper-11157363.
METHODS: We investigated the reinforcing effects of the fatty acid amide hydrolase ( FAAH) inhibitor URB597 in monkeys trained to intravenously self-administer Delta(9)-tetrahydrocannabinol ( THC), anandamide, or cocaine and quantified brain endocannabinoid levels using liquid chromatography/ mass spectrometry. Paper-13089880.
It is concluded that ibu-am5 is an analogue of ibuprofen with a greater potency towards fatty acid amide hydrolase but with a similar cyclooxygenase inhibitory profile, and may be useful for the study of the therapeutic potential of combined fatty acid amide hydrolase- cyclooxygenase inhibitors. Paper-13259774.
While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay. Paper-12674514.
Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others. Paper-10671056.
CONCLUSIONS: These results indicate that the integrity of the CB(1) receptors is necessary for the incentive motivation of the rats for nicotine and that FAAH inhibition may be as effective as CB(1) receptor blockade to prevent reinstatement of nicotine seeking. Paper-13904848.
The two well-established eCBs, N-arachidonoylethanolamide ( AEA) and 2-arachidonoylglycerol ( 2-AG), are produced by neurons on demand, act near their sites of synthesis and are effectively metabolized by fatty acid amide hydrolase ( FAAH) and monoglyceride lipase ( MGL), respectively. Paper-12513838.
The cannabinergic proteins currently being explored, which include the CB1 and CB2 receptors, FAAH and the anandamide transporter, are excellent targets for the development of therapeutically useful drugs for a range of conditions including pain, loss of appetite, immunosuppression, peripheral vascular disease and motor disorders. Paper-9595303.
OBJECTIVE: The aim of the study was to explore the effect of inhibiting FAAH enzyme by URB597 on nicotine self-administration under a progressive ratio schedule and reinstatement of nicotine seeking, in comparison with the effect of the CB(1) antagonist rimonabant. Paper-13904848.
However, new genetic and pharmacological tools are available to increase endocannabinoid levels by targeting fatty acid amide hydrolase ( FAAH) or monoacylglycerol lipase ( MAGL), the enzymes responsible for the degradation of the endogenous cannabinoid ligands anandamide and 2-arachidonoylglycerol, respectively. Paper-13821822.
Quantitative reverse transcription polymerase chain reaction after induction of experimental colitis by different pathways showed that expression of FAAH messenger RNA (mRNA) is significantly reduced in different models of inflammation early in the expression of colitis, and these return to control levels as the disease progresses. Paper-13085648.
After brain stimulation reward thresholds stabilized, rats received intraperitoneal injections of the fatty acid amide hydrolase ( FAAH) inhibitors phenylmethylsulfonyl fluoride ( PMSF) (0, 15, 30, and 60 mg/kg) and URB-597 (0, 0.3, 1, and 3 mg/kg) and the selective anandamide reuptake inhibitor OMDM-2 (0, 3, 10, and 30 mg/kg). Paper-12223583.
Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders: CNR1, CB2, FAAH, MGLL, TRPV1 and GPR55 and (b) genes from various neurotransmitter systems that are likely to exert a non-specific influence on risk of cannabis use disorders, e.g. GABRA2, DRD2 and OPRM1. Paper-13694127.
Mass spectrometry of subcellular membrane fractions revealed that the tritium accumulation observed in the caveolin-rich membrane fraction was not representative of intact anandamide, suggesting that following metabolism by the enzyme fatty acid amide hydrolase ( FAAH), anandamide metabolites are rapidly enriched in caveolae. Paper-10614952.
These head group constrained and conformationally restricted analogues of 2-AG as well as the 1-keto precursors were evaluated as substrates for the endocannabinoid deactivating hydrolytic enzymes monoacylglycerol lipase ( MGL) and fatty acid amide hydrolase ( FAAH), and also were tested for their affinities for CB1 and CB2 cannabinoid receptors. Paper-12563645.
BACKGROUND: The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine ( anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Paper-10825028.
Inhibitors of fatty acid amide hydrolase ( FAAH) increase endogenous levels of anandamide (a cannabinoid CB(1)-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain. Paper-13743637.
In addition, in vivo treatment with CBD markedly stimulated ( approximately 175%) the activity of fatty acid amide hydrolase ( FAAH), the main anandamide-degrading enzyme, while decreasing anandamide content ( approximately 30%) and binding to CB1 cannabinoid receptors ( approximately 25%). Paper-12712533.
ABSTRACT: BACKGROUND: Several lines of evidence indicate that the central cannabinoid receptor 1 ( CNR1) as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase ( FAAH), N-acylethanolamine-hydrolyzing acid amidase ( NAAA) and monoglyceride lipase ( MGLL) are implicated in mediating the orexigenic effects of cannabinoids. Paper-13503288.
In visceral adipose tissue, CB(1) mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Paper-12288922.
Here, we report that Hydra contains: (i) selective cannabinoid binding sites; (ii) the endogenous cannabinoid receptor ligand, anandamide (arachidonoylethanolamide); (iii) a fatty acid amide hydrolase-like activity catalysing anandamide hydrolysis; and (iv) the putative biosynthetic precursor of anandamide, N-arachidonoylphosphatidylethanolamine. Paper-1997356.
An alternative approach that can be used to harness the potential therapeutic effects of cannabinoids is to maximise the effects of the endocannabinoids, the actions of which are terminated by re-uptake and metabolism by various enzymes, including fatty acid amide hydrolase ( FAAH), monoacylglycerol lipase ( MAGL) and cyclooxygenase type 2 ( COX2). Paper-12584928.
Alternatively, inhibiting fatty acid amide hydrolase ( FAAH) and monoacylglycerol lipase ( MAGL), the principal enzymes responsible for the degradation of the respective endogenous cannabinoids, anandamide (AEA) and 2-arachydonylglycerol (2-AG), reduce nociception in a variety of nociceptive assays, with no or minimal behavioral effects. Paper-13944391.
In the present study, we investigated whether increasing endogenous cannabinoids levels, through the use of FAAH (-/-) mice as well as the FAAH inhibitor URB597 or the MAGL inhibitor JZL184, would reduce the intensity of withdrawal signs precipitated by the CB(1) receptor antagonist rimonabant in THC-dependent mice. Paper-13821822.
The most abundant endogenous endocannabinoid, anandamide, has been shown to activate the cannabinoid receptor type 1 ( CB1) and type 2 ( CB2) as well as the 'non-cannabinoid' transient receptor potential channel-vanilloid sub-family member 1 (TRPV1), before being rapidly metabolised by fatty acid amide hydrolase ( FAAH). Paper-12532849.
Selective inhibitors [arachidonoyl-serotonin (AA-5-HT) and URB597, 0-5 and 0-10 mg/kg, i.p.] of one of the major endocannabinoid metabolic enzymes, the intracellular fatty acid amide hydrolase ( FAAH), do not significantly prevent vomiting produced by emetic doses of i.p.-administered 2-AG, cisplatin or the dopamine receptor agonist apomorphine. Paper-11278072.
These synonyms are used for gene FAAH (fatty acid amide hydrolase): Oleamide hydrolase 1, MGC138146, MGC102823, Fatty-acid amide hydrolase 1, FAAH-1, FAAH1, Anandamide amidohydrolase 1.
These accession numbers are used for gene FAAH: Q9UG55 (UNIPROT__AC), Q52M86 (UNIPROT__AC), CAI21960 (NCBI_GENBANK__AC), AAB58505 (NCBI_GENBANK__AC).
FAAH is a homologue of NCU08356 (similar to acetamidase) from Neurospora crassa OR74A.
FAAH is a homologue of FAAH (fatty acid amide hydrolase) from Bos taurus.
FAAH is a homologue of FAAH (fatty acid amide hydrolase) from Pan troglodytes.
FAAH is a homologue of FAAH (fatty acid amide hydrolase) from Gallus gallus.
FAAH is a homologue of FAAH (fatty acid amide hydrolase) from Canis lupus familiaris.
FAAH is a homologue of Faah (fatty acid amide hydrolase) from Mus musculus.
FAAH is a homologue of Faah (fatty acid amide hydrolase) from Rattus norvegicus.
FAAH is a homologue of F58H7.2 (hypothetical protein) from Caenorhabditis elegans.
FAAH is a homologue of amidase (hypothetical protein) from Caenorhabditis elegans.
FAAH is a homologue of amidase (hypothetical protein) from Caenorhabditis elegans.
Important links !
iHOP - Information Hyperlinked over Proteins .
Concept & Implementation by Robert Hoffmann.