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.
The effect of lipopolysaccharide inhalation upon lung anandamide levels, anandamide synthetic enzymes and fatty acid amide hydrolase has been investigated. Lipopolysaccharide exposure produced a dramatic extravasation of neutrophils and release of tumour necrosis factor alpha into the bronchoalveolar lavage (BAL) fluid, which was not accompanied by epithelial cell injury. The treatment, however, did not change significantly the levels of anandamide and the related compound palmitoylethanolamide in the cell-free fraction of the BAL fluid. The activities of the anandamide synthetic enzymes N-acyltransferase and N-acylphosphatidylethanolamine phospholipase D and the activity of fatty acid amide hydrolase in lung membrane fractions did not change significantly following the exposure to lipopolysaccharide. The non-selective fatty acid amide hydrolase inhibitor phenylmethylsulfonyl fluoride was a less potent inhibitor of lung fatty acid amide hydrolase than expected from the literature, and a dose of 30 mg/kg i.p. of this compound, which produced a complete inhibition of brain anandamide metabolism, only partially inhibited the lung metabolic activity.
Holt
Sandra
S
Department of Pharmacology and Clinical Neuroscience, Umeå University, SE901 87 Umeå, Sweden. Sandra.Holt@pharm.umu.se
Rocksén
David
D
Bucht
Anders
A
Petersen
Gitte
G
Hansen
Harald S
HS
Valenti
Marta
M
Di Marzo
Vincenzo
V
Fowler
Christopher J
CJ
D000217:Acyltransferases / Q000378:metabolism; D000280:Administration, Inhalation; D000581:Amidohydrolases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D015536:Down-Regulation; D063388:Endocannabinoids; D005260:Female; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099252:Fatty Acid Amide Hydrolases
D000217:Acyltransferases; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D008070:Lipopolysaccharides; D010664:Phenylmethylsulfonyl Fluoride; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide