Chronic allergen exposure enhances cholinergic neurotransmission in sensitized guinea-pigs

Abstract

Airway hyperresponsiveness in asthmatic patients may be related to cholinergic hyperresponsiveness. In this study, we examined whether chronic allergen exposure induces cholinergic hyperresponsiveness in ovalbumin (OA) sensitized guinea-pig airways. Three weeks after active sensitization, ovalbumin (0.03%, for 3 min, challenged group) or saline inhalation (control group) was repeated every day for 4 weeks. Cholinergic responses were assessed by isometric tracheal contraction after electrical field stimulation (EFS) or exogenously applied acetylcholine (ACh). The contractions were expressed as a percentage of the maximum response to ACh (10(-3) M) (AChmax). We calculated the effective frequencies producing 25% of AChmax (EF25) from frequency-response curves. EFS-induced contractile responses were significantly enhanced in the challenged group (logEF25 = 0.66 +/- 0.08 (mean +/- SEM)) compared with the control group (logEF25 = 1.12 +/- 0.16). In contrast, exogenous ACh-mediated contractile tracheal responses were almost the same in both groups. We conclude that repeated allergen inhalation causes cholinergic airway hyperresponsiveness, presumably due to the facilitation of cholinergic neurotransmission. This mechanism may be involved in the airway hyperresponsiveness in asthmatic airways.