The role of the epithelium in modulating the responses of guinea-pig trachea induced by bradykinin in vitro.

1. The effect of removing the epithelium on the responses of the guinea-pig isolated trachea (GPT) to bradykinin (BK) and prostaglandin E2 (PGE2) was investigated. 2. BK (3 pmol-10 nmol) induced dose-related relaxations of the intact (with epithelium), and contracted the rubbed (without epithelium) preparation of GPT. Similar responses were also obtained with PGE2 (0.3-3.0 nmol). 3. Indomethacin (1.4 microM) modified the BK-induced response of intact GPT, from a relaxation to a contraction, but inhibited the BK-induced contraction of the rubbed GPT. 4. There was a significant increase in PGE2 release from the intact GPT following stimulation with BK. 5. Removal of the epithelium from the GPT significantly reduced both basal and BK-induced generation of PGE2. 6. The induction of tone in the rubbed GPT by addition of acetylcholine (ACh) caused BK and PGE2 (0.3 nmol-3 nmol) to produce relaxations of the tissue. 7. Salbutamol (10(-8) M-10(-6) M) reduced the relaxations induced by BK on intact GPT, in a concentration-dependent manner. 8. These results suggest that both tone and an epithelial-dependent cyclo-oxygenase mechanism are important in modulating BK-induced responses of GPT.