Endothelin-1 stimulates proliferation of normal airway epithelial cells.
To investigate the influence of endothelins on airway epithelial cell growth, we measured [3H]thymidine incorporation and cell numbers of cultured porcine tracheal epithelial cells in the presence or absence of endothelin-1 or -3 with or without PD-145065 (a combined endothelin-A and -B receptor antagonist), BQ-123 (an antagonist specific for endothelin-A receptors) or phosphoramidon (an inhibitor, in part, of endothelin converting enzymes). We found that endothelin-1 stimulated the proliferation of airway epithelial cells and this response was progressively inhibited by increasing concentrations of either PD-145065 or BQ-123. In contrast to endothelin-1, airway epithelial cells were not responsive to endothelin-3. They also appeared to be producing endothelin-1 endogenously. Phosphoramidon significantly decreased basal growth of cells incubated in the absence of exogenous endothelin, and was associated with a significant diminution in their endothelin production. We conclude that endothelin-1 is mitogenic for porcine airway epithelial cells and may be involved in both autocrine and paracrine control of them.
Murlas
C G
CG
Lung Cell Biology Laboratories, Rush University, Chicago, IL 60612, USA.
Gulati
A
A
Singh
G
G
Najmabadi
F
F
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D016232:Endothelins; D006020:Glycopeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; C082887:PD 145065; D004247:DNA; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon