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Gene Review

Faah  -  fatty acid amide hydrolase

Mus musculus

Synonyms: AW412498, Anandamide amidohydrolase 1, Faah1, Fatty-acid amide hydrolase 1, Oleamide hydrolase 1
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Disease relevance of Faah

  • Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Delta(6)-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis [1].
  • In order to test whether anandamide and other non-cannabinoid fatty amides modulate nociception, we compared FAAH (+/+) and (-/-) mice in the tail immersion, hot plate, and formalin tests, as well as for thermal hyperalgesia in the carrageenan and the chronic constriction injury (CCI) models [2].
  • Here we show that mice lacking the enzyme fatty acid amide hydrolase (FAAH(-/-)) are severely impaired in their ability to degrade anandamide and when treated with this compound, exhibit an array of intense CB(1)-dependent behavioral responses, including hypomotility, analgesia, catalepsy, and hypothermia [3].
  • These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB1 agonists [4].
  • When using FAAH preparations from mouse neuroblastoma N18TG2 cells and [14C]anandamide as a substrate, the IC50s for these compounds ranged from 12.0 to 26 microM, the most active compound being AA-5-HT [5].

Psychiatry related information on Faah

  • Therefore, our primary goal was to determine whether FAAH (-/-) mice, which possess elevated levels of anandamide and other FAAs, would display altered performance in four Morris water maze tasks: acquisition of a hidden fixed platform, reversal learning, working memory, and probe trials [6].
  • MEASUREMENTS AND RESULTS: FAAH (-/-) mice possess higher values of slow-wave sleep and more intense episodes of slow-wave sleep than do control littermates under baseline conditions that are not related to differences in Tb and LMA [7].
  • To determine if, in the absence of FAAH, the hypnogenic fatty acid amides induce an increase of sleep, we characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation [7].
  • DESIGN: FAAH (-/-), FAAH (+/-), and FAAH (+/+) mice were implanted chronically for sleep, body temperature (Tb), and locomotor activity (LMA) recordings [7].

High impact information on Faah


Chemical compound and disease context of Faah


Biological context of Faah

  • No sequence abnormality was detected in PCR products containing the 15 exons and splice junctions of the mouse Faah gene [12].
  • Analysis of an SCH mapping panel and a mouse interspecific backcross panel has localized the Faah gene to the conserved syntenic region on mouse chromosome 4, close to the neurological mutation clasper [12].
  • Faah gene rearrangements were excluded by Southern blot analysis of clasper DNA [12].
  • In contrast, no genotype differences in pain behavior were evident following CCI, which was instead found to obliterate the phenotypic hypoalgesia displayed by FAAH (-/-) mice in the tail immersion and hot plate tests, suggesting that nerve injury may promote adaptive changes in these animals [2].
  • Collectively, these findings demonstrate a cannabinoid receptor-mediated analgesic phenotype in FAAH (-/-) mice [2].

Anatomical context of Faah

  • METHODS: Motility was measured by evaluating the distribution of a fluorescent marker along the small intestine; FAAH messenger RNA (mRNA) levels were analyzed by reverse-transcription polymerase chain reaction (RT-PCR); endocannabinoid levels were measured by isotope-dilution, liquid chromatography, mass spectrometry [9].
  • Finally, there are regions of the brain where FAAH-immunoreactive neurons and/or oligodendrocytes occur in the absence of CB(1)-immunoreactive fibers and here FAAH may be involved in regulation of signaling mediated by other endocannabinoid receptors or by receptors for other fatty acid amide signaling molecules [13].
  • In many regions of the brain, a complementary pattern of FAAH and CB(1) expression was observed, with FAAH-immunoreactive neuronal somata and dendrites surrounded by CB(1)-immunoreactive fibers [13].
  • Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells [14].
  • However, in some regions of the brain such as the globus pallidus and substantia nigra pars reticulata, CB(1) receptors are abundant but with little or no associated FAAH expression and in these brain regions the spatial impact and/or duration of endocannabinoid signaling may be less restricted than in regions enriched with FAAH [13].

Associations of Faah with chemical compounds


Enzymatic interactions of Faah


Regulatory relationships of Faah


Other interactions of Faah

  • This complementary pattern of FAAH and CB(1) expression provided the basis for a hypothesis that endocannabinoids may function as retrograde signaling molecules at synapses in the brain [Proc R Soc Lond B 265 (1998) 2081; Phil Trans R Soc Lond 356 (2001) 381] and subsequent experimental studies have confirmed this [Science 296 (2002) 678] [13].
  • Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension [4].
  • Methylation of the amide group decreased the activity at VR1, AMT, and FAAH [18].
  • As previously reported, Northern blot hybridization detected a transcript of approximately 2.5 kilobases of FAAH mRNA in whole uterine poly(A)+ RNA samples [19].
  • Fatty acid amide hydrolase in brain ventricular epithelium: mutually exclusive patterns of expression in mouse and rat [20].

Analytical, diagnostic and therapeutic context of Faah


  1. The endogenous cannabinoid system protects against colonic inflammation. Massa, F., Marsicano, G., Hermann, H., Cannich, A., Monory, K., Cravatt, B.F., Ferri, G.L., Sibaev, A., Storr, M., Lutz, B. J. Clin. Invest. (2004) [Pubmed]
  2. Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia. Lichtman, A.H., Shelton, C.C., Advani, T., Cravatt, B.F. Pain (2004) [Pubmed]
  3. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Cravatt, B.F., Demarest, K., Patricelli, M.P., Bracey, M.H., Giang, D.K., Martin, B.R., Lichtman, A.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase. Pacher, P., Bátkai, S., Osei-Hyiaman, D., Offertáler, L., Liu, J., Harvey-White, J., Brassai, A., Járai, Z., Cravatt, B.F., Kunos, G. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  5. Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. Bisogno, T., Melck, D., De Petrocellis, L., Bobrov MYu, n.u.l.l., Gretskaya, N.M., Bezuglov, V.V., Sitachitta, N., Gerwick, W.H., Di Marzo, V. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  6. Fatty acid amide hydrolase (-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze task. Varvel, S.A., Cravatt, B.F., Engram, A.E., Lichtman, A.H. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  7. Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolase. Huitron-Resendiz, S., Sanchez-Alavez, M., Wills, D.N., Cravatt, B.F., Henriksen, S.J. Sleep. (2004) [Pubmed]
  8. Fatty acid amide hydrolase deficiency limits early pregnancy events. Wang, H., Xie, H., Guo, Y., Zhang, H., Takahashi, T., Kingsley, P.J., Marnett, L.J., Das, S.K., Cravatt, B.F., Dey, S.K. J. Clin. Invest. (2006) [Pubmed]
  9. Fatty acid amide hydrolase controls mouse intestinal motility in vivo. Capasso, R., Matias, I., Lutz, B., Borrelli, F., Capasso, F., Marsicano, G., Mascolo, N., Petrosino, S., Monory, K., Valenti, M., Di Marzo, V., Izzo, A.A. Gastroenterology (2005) [Pubmed]
  10. Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. Lichtman, A.H., Hawkins, E.G., Griffin, G., Cravatt, B.F. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  11. Characterization of the 5'-sequence of the mouse fatty acid amide hydrolase. Puffenbarger, R.A., Kapulina, O., Howell, J.M., Deutsch, D.G. Neurosci. Lett. (2001) [Pubmed]
  12. Conserved chromosomal location and genomic structure of human and mouse fatty-acid amide hydrolase genes and evaluation of clasper as a candidate neurological mutation. Wan, M., Cravatt, B.F., Ring, H.Z., Zhang, X., Francke, U. Genomics (1998) [Pubmed]
  13. Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Egertová, M., Cravatt, B.F., Elphick, M.R. Neuroscience (2003) [Pubmed]
  14. Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Cobellis, G., Cacciola, G., Scarpa, D., Meccariello, R., Chianese, R., Franzoni, M.F., Mackie, K., Pierantoni, R., Fasano, S. Biol. Reprod. (2006) [Pubmed]
  15. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. Bilsland, L.G., Dick, J.R., Pryce, G., Petrosino, S., Di Marzo, V., Baker, D., Greensmith, L. FASEB J. (2006) [Pubmed]
  16. Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake. Ortega-Gutiérrez, S., Hawkins, E.G., Viso, A., López-Rodríguez, M.L., Cravatt, B.F. Biochemistry (2004) [Pubmed]
  17. Characterization of palmitoylethanolamide transport in mouse Neuro-2a neuroblastoma and rat RBL-2H3 basophilic leukaemia cells: comparison with anandamide. Jacobsson, S.O., Fowler, C.J. Br. J. Pharmacol. (2001) [Pubmed]
  18. A structure/activity relationship study on arvanil, an endocannabinoid and vanilloid hybrid. Di Marzo, V., Griffin, G., De Petrocellis, L., Brandi, I., Bisogno, T., Williams, W., Grier, M.C., Kulasegram, S., Mahadevan, A., Razdan, R.K., Martin, B.R. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  19. Fatty-acid amide hydrolase is expressed in the mouse uterus and embryo during the periimplantation period. Paria, B.C., Zhao, X., Wang, J., Das, S.K., Dey, S.K. Biol. Reprod. (1999) [Pubmed]
  20. Fatty acid amide hydrolase in brain ventricular epithelium: mutually exclusive patterns of expression in mouse and rat. Egertová, M., Michael, G.J., Cravatt, B.F., Elphick, M.R. J. Chem. Neuroanat. (2004) [Pubmed]
  21. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Gobbi, G., Bambico, F.R., Mangieri, R., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M.G., Debonnel, G., Duranti, A., Tontini, A., Tarzia, G., Mor, M., Trezza, V., Goldberg, S.R., Cuomo, V., Piomelli, D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  22. Lipopolysaccharide-induced pulmonary inflammation is not accompanied by a release of anandamide into the lavage fluid or a down-regulation of the activity of fatty acid amide hydrolase. Holt, S., Rocksén, D., Bucht, A., Petersen, G., Hansen, H.S., Valenti, M., Di Marzo, V., Fowler, C.J. Life Sci. (2004) [Pubmed]
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