title: N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase.
abstract: Anandamide ( N-arachidonoylethanolamine) and other bioactive N-acylethanolamines are degraded to their corresponding fatty acids and ethanolamine. This hydrolysis is mostly attributed to catalysis by FAAH (fatty acid amide hydrolase), which exhibits an alkaline pH optimum. In addition, we have identified another amidase which catalyses the same reaction exclusively at acidic pH values [Ueda, Yamanaka and Yamamoto (2001) J. Biol. Chem. 276, 35552-35557]. In attempts to find selective inhibitors of this acid amidase, we screened various derivatives of palmitic acid, 1-hexadecanol, and 1-pentadecylamine with N-palmitoylethanolamine as substrate. Here we show that N-cyclohexanecarbonylpentadecylamine inhibits the acid amidase from rat lung with an IC50 of 4.5 microM, without inhibiting FAAH at concentrations up to 100 microM. The inhibition was reversible and non-competitive. This compound also inhibited the acid amidase in intact alveolar macrophages. With the aid of this inhibitor, it was revealed that rat basophilic leukaemia cells possess the acid amidase as well as FAAH. Thus the inhibitor may be a useful tool to distinguish the acid amidase from FAAH in various tissues and cells and to elucidate the physiological role of the enzyme.
authors.affiliation: Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Christine
authors.initials: C
authors.lastname: Hilligsmann
authors.forename: Séverine
authors.initials: S
authors.lastname: Vandevoorde
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000581:Amidohydrolases / Q000032:analysis / Q000037:antagonists & inhibitors*; D000818:Animals; D045744:Cell Line, Tumor / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D004983:Ethanolamines; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000201:enzymology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009928:Organ Specificity; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D009363:Neoplasm Proteins; D010169:Palmitic Acids; D000099252:Fatty Acid Amide Hydrolases; C487720:N-cyclohexanecarbonylpentadecylamine; C005958:palmidrol; C478603:N-palmitoylethanolamine-selective acid amidase