Modulation by the epithelium of the extent of bronchial narrowing produced by substances perfused through the lumen

Abstract

1 Airway narrowing was determined in vitro as a measure of bronchial reactivity. A bronchial segment from pig lung was perfused with a Krebs solution and the change in flow rate to drugs and small ions perfused intraluminally was compared with that obtained by application to the serosal surface. 2 The sensitivity (EC50) to acetylchloline was 30 times greater on the serosal surface than on the luminal surface. Concentrations of histamine and carbachol which had threshold responses on flow rate when perfused intraluminally virtually stopped flow on the serosal surface. Potassium depolarizing solutions (containing either KCl or K2SO4) and vanadate (VO3-) had little or no effect intraluminally but completely stopped flow through the bronchial segment when applied to the serosal surface, i.e. they closed off the airway. 3 After removal of the epithelium the sensitivity to drugs and K+ perfused intraluminally was increased to equal that on the serosal surface. 4 No evidence for suppression of smooth muscle contraction by a putative epithelium-derived inhibitory factor (EpDIF) could be obtained: no inhibition of smooth muscle contractility was seen when the agents listed above were perfused intraluminally and their perfusion continued while they were applied to outside. 5 It was concluded that the epithelium plays a crucial role as an impermeant barrier in modulating the responsiveness of the airways smooth muscle.