Epithelium-derived PGE2 inhibits the contractile response to cholinergic stimulation in isolated ferret trachea

We have previously reported that epithelium-dependent inhibitory factors, both prostanoids and non-prostanoids, can be activated by electrical field stimulation (EFS) and direct nerve stimulation (DNS) in an in vitro nerve-muscle preparation of ferret trachea. In this study we set out to compare the release of the inhibitory prostanoids, PGE2 and PGI2, in preparations with intact and with removed epithelium. Ferret tracheae were mounted in organ baths and phasic contractions were induced by EFS and DNS. The bath concentrations of PGE2 and the PGI2-metabolite 6-keto-PGF1 alpha were measured using radioimmuno assays. The gradual decrease in contractile response to DNS, 2 Hz for 120 min, was 95 +/- 2% of baseline (mean +/- SEM) in preparations with intact epithelium compared with 29 +/- 8% in epithelium-denuded preparations (p less than 0.001). The bath-levels of PGE2 showed a slight but significant (p less than 0.01) increase in denuded preparations with a final bath-concentration at 120 min of 13 +/- 3 pg/ml. The release of PGE2 was more pronounced in preparations with intact epithelium which resulted in a final bath-concentrations of PGE2 of 84 +/- 38 pg/ml which was significantly higher compared with epithelium-denuded preparations and also compared with time-matched controls with the same pattern of contraction induced by DNS alone. The concentrations of 6-keto-PGF1 alpha showed a slight increase which was of comparable magnitude (ns) in intact and denuded preparations. In conclusion this study demonstrates that the cyclooxygenase-dependent component of the epithelium-dependent inhibition of the contractile response to cholinergic nerve stimulation in ferret trachea is mediated by PGE2 but not by PGI2.