A novel pharmacologic action of glucocorticosteroids on leukotriene C4 catabolism.
Leukotriene (LT) C(4), a potent chemical mediator in human bronchial asthma, is metabolized to less active LTE(4) via LTD(4) in 2 consecutive enzymatic reactions by gamma-glutamyl transpeptidases and dipeptidases. We examined whether this inactivation process of LTC(4) was affected by fluticasone propionate, beclomethasone dipropionate, disodium cromoglycate, and salbutamol sulfate in transformed human bronchial epithelial cells. Fluticasone propionate and beclomethasone dipropionate accelerated LTC(4) catabolism by inducing activity of a LTC(4)-degrading enzyme, gamma-glutamyl transpeptidase-related enzyme (gamma-GTPRE), in transformed human bronchial epithelial cells. The activation of gamma-GTPRE might be regulated transcriptionally. This is a novel regulatory mechanism by which glucocorticosteroids exert antiasthma activities.
Zaitsu
M
M
Departments of Pediatrics and Internal Medicine, Saga Medical School, Saga, Japan.
Hamasaki
Y
Y
Aoki
Y
Y
Miyazaki
S
S
D000420:Albuterol / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001507:Beclomethasone / Q000494:pharmacology; D002461:Cell Line, Transformed; D004205:Cromolyn Sodium / Q000494:pharmacology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis / Q000235:genetics
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D017997:Leukotriene C4; D000068298:Fluticasone; D005723:gamma-Glutamyltransferase; D001507:Beclomethasone; D004205:Cromolyn Sodium; D000420:Albuterol