The influence of epithelium on the responsiveness of guinea-pig isolated trachea.

This study was designed to investigate the possibility that tracheal epithelium generates a relaxant factor analogous to the endothelial-derived relaxant factor (EDRF) of vascular tissue. The absence of such a factor following epithelial damage in diseases such as asthma might help to explain the airway hyperreactivity characteristic of such diseases. Removal of epithelium by rubbing enhanced the sensitivity of guinea-pig isolated tracheal chains to 5-hydroxytryptamine, histamine, acetylcholine, adenosine, isoprenaline and also minimally to KCl. Responses to LaCl3 and electrical field stimulation were not affected. Low concentrations of adenosine produced contractions only in tissues denuded of epithelium. In the presence of indomethacin 1.4 microM or dithiothreitol (DTT) 1 microM, dose-response curves to histamine were moved to the left in both control and rubbed tissues, and the maximum response was increased. The difference in sensitivity between tissues with and without epithelium was not affected by indomethacin, but was slightly reduced by DTT. Phenidone (0.1 mM) also increased the maximum responses, but increased the sensitivity only of the tissues with intact epithelium, to the same level as that seen in the tissues denuded of epithelium. Superfusion cascade studies provided no evidence for the generation of a relaxant factor from tracheal epithelium. It is suggested that the supersensitivity produced by removal of the epithelium is not due to the removal of a relaxant factor, but rather to the removal of a permeability barrier, allowing a greater concentration of agonist at the level of the underlying smooth muscle.