Differences in the pharmacological properties of rat and chicken brain fatty acid amidohydrolase.
The pharmacological properties of fatty acid amidohydrolase (FAAH) were investigated in brains of 35-day-old chickens, since nothing is known about the enzyme in avian species. FAAH activity towards both [(3)H]-palmitoylethanolamide (PEA) [K(M)=1.5 microM] and [(3)H]-anandamide (AEA) [K(M)=5.4 microM] was demonstrated in the chicken brains. The chicken FAAH was inhibited by the substrate analogues oleyl trifluoromethylketone (OTMK) and diazomethylarachidonyl ketone (DAK) with similar potencies to the rat FAAH. However, in contrast to the rat brain, phenylmethylsulphonyl fluoride (PMSF) and the enantiomers of ibuprofen had very weak effects on chicken brain FAAH. Indomethacin and niflumic acid were found to inhibit rat brain AEA hydrolysis. The inhibition by indomethacin was reversible and competitive, with a K(i) value of 120 microM. Chicken FAAH was less sensitive to indomethacin than its rodent counterpart, but the inhibition was also competitive (K(i)). It is concluded that chicken FAAH activity has different pharmacological properties to its rodent counterpart.
Fowler
C J
CJ
Department of Pharmacology and Clinical Neuroscience, Umeâ University, SE-901 87 Umeâ, Sweden. cf@pharm.umu.se
Börjesson
M
M
Tiger
G
G
D000581:Amidohydrolases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002645:Chickens; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D003978:Diazomethane; D004791:Enzyme Inhibitors; D007052:Ibuprofen; D007213:Indomethacin; D010664:Phenylmethylsulfonyl Fluoride; D000099252:Fatty Acid Amide Hydrolases; C113377:diazomethylarachidonyl ketone