Contractions of canine intrapulmonary airways and their dependence on choline uptake

The importance of high-affinity choline uptake in sustaining the synthesis of acetylcholine in isolated canine intrapulmonary airways was examined by using tissue bath techniques. Prolonged electrical stimulation of control airways caused contractions that decayed during the first few minutes of stimulation but eventually reached plateaus. In contrast, contractions decayed rapidly in airways exposed to 10(-4) M hemicholinium-3. Exogenously administered choline (10(-4) M), neostigmine (2 X 10(-6) M) and physostigmine (2 X 10(-6) M) all caused contractions of resting airways, which we conclude were mediated by the spontaneous release of acetylcholine because these responses were abolished by atropine and hemicholinium-3. Thus, the store of acetylcholine involved in spontaneous release could be abolished rapidly by hemicholinium-3, but sufficient acetylcholine remained for normal responses to brief periods of nerve stimulation. This differential depletion indicates that the acetylcholine involved in spontaneous release may originate from a different intraneuronal site than the vesicular acetylcholine involved in the exocytotic process that occurs during nerve stimulation.