Adrenergic neurotransmission in airways: inhibition by acetylcholine

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Abstract
Superfusion techniques were used to examine the effect of acetylcholine (ACh) on the release of norepinephrine (NE) from isolated dog airways. Trachealis strips and helical strips of intrapulmonary airways were incubated with 3H-labeled NE, rinsed and mounted in superfusion chambers. The superfusate was collected at timed intervals for estimation of total radioactivity and for column chromatographic separation of NE and its metabolites. Field electrical stimulation (2 Hz) and tyramine perfusion (3 .times. 10-5 M) increased the total radioactivity of the perfusate by increasing the amount of intact 3H-labeled NE and the amounts of all metabolic fractions. Extraneuronal and neuronal uptake mechanisms were important in inactivating the NE released by either stimulus. Exogenously administered ACh (10-6-10-5 M) inhibited the release of NE that was caused by nerve stimulation but not that caused by tyramine perfusion. The inhibitory effect of ACh was antagonized by atropine (10-6 M) but not by hexamethonium (5 .times. 10-6 M). ACh inhibits the exocytotic nerve-stimulated NE release by activating muscarinic receptors on adrenergic nerve varicosities.