title: Anandamide degradation and N-acylethanolamines level in wild-type and CB1 cannabinoid receptor knockout mice of different ages.
abstract: CD1 mice lacking the CB1 receptors (knockout, KO) were compared with wild-type littermates for their ability to degrade N-arachidonoylethanolamine (anandamide, AEA) through a membrane transporter (AMT) and a fatty acid amide hydrolase (FAAH). The regional distribution and age-dependence of AMT and FAAH activity were investigated. Anandamide membrane transporter and FAAH increased with age in knockout mice, whereas they showed minor changes in wild-type animals. Remarkably, they were higher in all brain areas of 6-month-old knockout versus wild-type mice, and even higher in 12-month-old animals. The molecular mass (approximately 67 kDa) and isoelectric point (approximately 7.6) of mouse brain FAAH were determined and the FAAH protein content was shown to parallel the enzyme activity. The kinetic constants of AMT and FAAH in the cortex of wild-type and knockout mice at different ages suggested that different amounts of the same proteins were expressed. The cortex and hippocampus of wild-type and knockout mice contained the following N-acylethanolamines: AEA (8% of total), 2-arachidonoylglycerol (5%), N-oleoylethanolamine (20%), N-palmitoylethanolamine (53%) and N-stearoylethanolamine (14%). These compounds were twice as abundant in the hippocampus as in the cortex. Minor differences were observed in AEA or 2-arachidonoylglycerol content in knockout versus wild-type mice, whereas the other compounds were lower in the hippocampus of knockout versus wild-type animals.
authors.affiliation: Departments of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Italy. Maccarrone@med.uniroma2.it
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: M
authors.initials: M
authors.lastname: Attinà
authors.forename: M
authors.initials: M
authors.lastname: Bari
authors.forename: A
authors.initials: A
authors.lastname: Cartoni
authors.forename: C
authors.initials: C
authors.lastname: Ledent
authors.forename: A
authors.initials: A
authors.lastname: Finazzi-Agrò
mesh_terms: D000375:Aging; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000493:pharmacokinetics*; D001692:Biological Transport; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002186:Cannabinoids / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism; D063388:Endocannabinoids; D004983:Ethanolamines / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism; D009928:Organ Specificity; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D002186:Cannabinoids; D002352:Carrier Proteins; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D018377:Neurotransmitter Agents; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide