The role of epithelium in the modulation of contractile responses to electrical field stimulation (EFS), acetylcholine (ACh), and KCl were studied in vitro in strips of equine tracheal smooth muscle (TSM). EFS with 0.5 ms pulses of voltage (70 V) resulted in frequency dependent contractions of equine TSM that were sensitive to tetrodotoxin (TTX) and atropine. In TSM without epithelium, preincubation with indomethacin significantly potentiated contractile responses to EFS. The potentiating effect of indomethacin on EFS contractions was abolished by the addition of 3 nM prostaglandin E2 (PGE2). ACh and KCl cumulative concentration-response curves were shifted to the left by removal of epithelium from equine TSM strips with a significant decrease in the 50% effective concentration (EC50) for both ACh and KCl. The mean EC50 (± SE) for ACh in TSM without epithelium was 0.51 ± 0.09 μM vs 4.30 ± 1.03 μM in TSM with epithelium. Similarly, the mean EC50 (± SE) for KCl in TSM without epithelium was 22.20 ± 2.61 mM vs 32.35 ± 2.66 mM in TSM with epithelium. The addition of indomethacin (3 μM) had no effect on the ACh concentration-response curves in TSM strips with or without epithelium. Our results suggest that in the equine airway there is (1) an epithelial-derived relaxant factor that modulates tracheal smooth muscle contractility postsynaptically, and (2) a nonepithelial-derived inhibitory factor, possibly PGE2, that modulates ACh release from nerves presynaptically.
Bibliographical noteFunding Information:
Support Grant from the NIH. We, especially want to thank Dr David R. Brown for helpful discussions and Dr Brad Gordon for his help and support. We also wish to thank Dr Vic Cox, Jim Malone, Duane Weiss and members of the Large Animal Clinical Sciences department for their help with this project. Petra Lackner was recipient of a UROP award from, the University of Minnesota.
Acknowledgements.T his work was supported by the Cystic Fibrosis Foundation and a Biomedical Research
- Prostaglandin, and tracheal smooth muscle
- Tracheal smooth muscle