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.