EPITHELIAL DISRUPTION BY PROTEASES AUGMENTS THE RESPONSIVENESS OF PORCINE BRONCHIAL SEGMENTS

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Abstract
1. The effect of disruption to the epithelium of intact porcine bronchi was examined by comparing the responsiveness to agonists applied to the adventitial and luminal surfaces. The development of smooth muscle tone was measured as an increase in pressure in an isovolumic bronchial segment of approximately 2 mm i.d. The reactivity and sensitivity to acetylcholine (ACh) introduced intraluminally was greatly attenuated when compared with adventitial addition. 2. Luminal exposure to K+ and vanadate (VO3-) had little effect compared with strong responses obtained by adventitial application. 3. Intraluminal exposure to trypsin, chymotrypsin and elastase (1 mg/mL) selectively augmented both the sensitivity and the reactivity to the luminal addition of ACh, K+ and carbachol. 4. Mechanical removal of the epithelium produced a 716-fold increase in sensitivity to ACh introduced luminally but had no effect on ACh applied adventitially. 5. The inhibitory effects of luminally introduced isoprenaline on electrical field stimulation responses were also significantly potentiated in segments stripped of epithelium. 6. The evidence presented here indicates that the responsiveness of in vitro airways segments is highly influenced by the epithelial layer, which acts most prominently as a barrier inhibiting the penetration of luminally introduced agonists.