Factors that determine acetylcholine responsiveness of guinea pig trachealtubes

Acetylcholine administered to the inside of epithelium-denuded tracheal tub es did cause a potent contraction (2486 +/- 120 me). In contrast, a respons e was hardly observed in tissues with an intact epithelial layer (674 +/- 8 1 mg), which was due to both the synthesis of nitric oxide and the activity of acetylcholinesterase, since the contractions to acetylcholine were sign ificantly enhanced after preincubation with N-omega-nitro-L-arginine methyl ester (L-NAME) or physostigmine (1374 +/- 65 and 1120 +/- 65 mg, respectiv ely). In addition, the suppressive effect was caused by the barrier functio n of the epithelial layer, since preincubation of epithelium-denuded tissue s with physostigmine significantly increased the pD(2) value for acetylchol ine (7.48 +/- 0.04) compared to intact tissues preincubated with physostigm ine (6.32 +/- 0.10) and epithelium-denuded preparations without physostigmi ne (6.37 +/- 0.06). Increasing concentrations of physostigmine administered to the inside of tissues with epithelium did induce a potent spontaneous c ontraction (1440 +/- 350 mg) that was prevented by atropine. In contrast to what was expected, the contractile response was diminished in tracheal tub es without epithelium (665 +/- 211 mg). It is concluded that contractions o f epithelium-denuded tissues are more pronounced to exogenous than to endog enous acetylcholine, and that the production and breakdown of this neurotra nsmitter is very rapid in intact guinea pig airways. Moreover, the release of nitric oxide and the barrier function of the epithelium did suppress the responsiveness to acetylcholine. (C) 2001 Elsevier science B.V. All rights reserved.