Incubation with IgE increases cholinergic neurotransmission in human airways in vitro.
Airway cholinergic hyperresponsiveness is frequently observed in asthmatic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertain. In this study, we examined whether incubation with IgE could facilitate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh), and they were assessed by isometric tension measurement. EFS-induced ACh release from cholinergic nerves was also measured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release as compared with the values of the bronchi incubated with heat inactivated IgE (control) (p < 0.05, respectively), but it did not alter the contractile responses induced by exogenous ACh. Pretreatment with the muscarinic M2-receptor agonist pilocarpine reduced the EFS-induced ACh release in the control tissues (p < 0.05), but not in the tissues incubated with IgE. The M2-receptor antagonist methoctramine significantly 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 cholinergic bronchial contraction via facilitation of ACh release from cholinergic nerves and that this augmentation is related to autoreceptor M2 dysfunction at nerve endings.
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
M
M
Ichinose
M
M
Miura
M
M
Tomaki
T
T
Oyake
N
N
Kageyama
Y
Y
Ikarashi
Y
Y
Maruyama
K
K
Shirato
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects; D004558:Electric Stimulation; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D066298:In Vitro Techniques; D008875:Middle Aged; D010277:Parasympathomimetics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D010277:Parasympathomimetics; D010862:Pilocarpine; D007073:Immunoglobulin E; D000109:Acetylcholine