Dexamethasone and phosphoramidon inhibit endothelin release by cultured nonciliated bronchiolar epithelial (Clara)...

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.