We investigated the effects of epithelial cells on excitatory cholinergic neurotransmission in dog trachea, to shed more light on the role of airway epithelial cells in regulating airway responsiveness. Airway epithelial cells were prepared by an enzymatic dissociation of the tracheal mucosa using protease-free collagenase. Tracheal smooth muscle contractions evoked by electrical field stimulation (EFS) or acetylcholine (ACh) were measured before and after the application of epithelial cells. Isolated and dispersed epithelial cells (3 × 105 cells/ml) suppressed the amplitude of the twitch-like contractions evoked by EFS in the combined presence of guanethidine sulfate (10-6m) and indomethacin (10-5m). In contrast, epithelial cells did not affect the contraction evoked by exogenously applied ACh. Atropine (10-6m) or tetrodotoxin (10-7m) abolished the contraction evoked by electrical field stimulation. These findings indicate that airway epithelial cells inhibit the excitatory neurotransmission of the vagus nerve, presumably by suppressing the release of ACh. Airway epithelial cells may therefore play an important role in regulating the response of smooth muscle.
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