An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins.

1. To examine the role of epithelium in the responsiveness of tracheal smooth muscle in rabbit, we measured the contractile responses to acetylcholine (ACh), KCl, 5-hydroxytryptamine (5-HT), histamine, substance P (SP), neurokinin A (NKA), and electrical field stimulation EFS) in intact and epithelium-denuded preparations. 2. Removal of epithelium did not alter the contractile response to any agonist examined, except SP. 3. Removal of epithelium enhances the contractile response to SP. In the presence of phosphoramidon, the contractile response to SP was not significantly different in either group. The results suggest that the effect of epithelium is largely due to degradation of SP by enzymes in the epithelium. 4. Arachidonic acid metabolites did not seem to be related to the responses induced by contractile agonists or EFS. 5. In the presence of SP, the contractile responses and [3H]-choline outflow evoked by EFS were dose-dependently enhanced. Contractile responses to EFS and [3H]-choline outflow evoked by EFS were enhanced by SP significantly more than by NKA. Both were abolished by atropine or tetrodotoxin. 6. These results suggest that rabbit tracheal epithelium may modulate SP-induced contractions, both direct and indirect, by inactivation of SP. This phenomenon is widespread in mammals. The rabbit may be a useful model to examine airway cholinergic functions.