Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle

The influence of the epithelium on the reactivity of guinea-pig tracheal smooth muscle in vitro was investigated. Mechanical removal of the epithelium produced contrasting effects on methacholine-, histamine- and K+-induced contractions of tracheal strips. Epithelium removal resulted in 2.1-fold shifts to the left of histamine and methacholine concentration-response curves, and an increase in the maximum response to histamine; the maximum response to methacholine was unaffected. Epithelium removal had little effect on the sensitivity, but decreased the maximum response to K+. The results suggest that inhibitory and excitatory factor(s) are released from epithelial cells, and that these factors modulate the reactivity of the smooth muscle. Indomethacin (1 microM) produced in epithelium-containing preparations qualitatively identical effects on the sensitivity to methacholine and on the maximum response to histamine as removal of the epithelium. However, indomethacin was without effect on the sensitivity to histamine in the presence or absence of the epithelium. Alterations in the production or release of epithelial cell-derived factors may contribute to the airway hyperreactivity observed in respiratory disorders.