Dexamethasone and phosphoramidon inhibit endothelin release by cultured nonciliated bronchiolar epithelial (Clara) cells.
The release of immunoreactive endothelin (ir-ET) by cultured Clara cells isolated from guinea pig lung was investigated. Clara cells were cultured in DMEM-F12 with 10% fetal bovine serum for 4-5 days. The basal release of ir-ET, measured by radioimmunoassay, from cultured guinea pig Clara cells incubated for 2, 6, and 10 h was 59.6 +/- 8.6, 206.0 +/- 25.0, and 291.0 +/- 16.5 pg/ml, respectively. Treatment with phosphoramidon (1 mM) for 45 min decreased the release of ir-ET by 73% and 76% in 6- and 10-h incubation periods, respectively. In addition, treatment with dexamethasone (1 microM) for 24 h significantly attenuated the release of ir-ET by 62% and 71% during 6- and 10-h incubation periods, respectively. Our results show that Clara cells isolated from guinea pig can synthesize significant amounts of ir-ET and that a phosphoramidon-sensitive metalloprotease appears to be responsible for the generation of endothelin. This basal release of ir-ET was significantly attenuated by dexamethasone.
Laporte
J
J
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
D'Orléans-Juste
P
P
Singh
G
G
Sirois
P
P
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D016232:Endothelins / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D011480:Protease Inhibitors / Q000494:pharmacology*
D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D003907:Dexamethasone; C008890:phosphoramidon