INCUBATION WITH IGE INCREASES CHOLINERGIC NEUROTRANSMISSION IN HUMAN AIRWAYS IN-VITRO

Airway cholinergic hyperresponsiveness is frequently observed in asthm atic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertai n. In this study, we era mined whether incubation with IgE could facil itate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile r esponses were induced by electrical field stimulation (EFS) or exogeno us acetylcholine (ACh), and they were assessed by isometric tension me asurement. EFS-induced ACh release from cholinergic nerves was also me asured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh relea se as compared with the values of the bronchi incubated with heat inac tivated IgE (control) (p < 0.05, respectively), but it did not alter t he contractile responses induced by exogenous ACh. Pretreatment with t he muscarinic M(2)-receptor agonist pilocarpine reduced the EFS-induce d ACh release in the control tissues (p < 0.05), but not in the tissue s incubated with IgE. The M(2)-receptor antagonist methoctramine signi ficantly enhanced the EFS-induced contraction in control bronchi (p < 0.05), but this augmentation was not observed in the tissues incubated with IgE. These results suggest that IgE itself can enhance cholinerg ic bronchial contraction via facilitation of ACh release from choliner gic nerves and that this augmentation is related to autoreceptor M(2) dysfunction at nerve endings.