Antigen-induced bronchial hyperresponsiveness in the rabbit is not dependent on M2-receptor dysfunction

We have assessed the effect of sensitization to allergen on airway smooth muscle responsiveness and acetylcholine (ACh) release from cholinergic nerves in tracheal preparations from rabbits immunized at birth to Alternaria tenuis and littermate control rabbits injected with saline. ACh release induced by EFS was significantly greater in tracheal preparations obtained from immunized rabbits compared with littermate controls. The ability of the muscarinic-receptor agonist, oxotremorine, to inhibit ACh release to EFS (4 Hz) was not altered by immunization. The contractile response evoked by electrical field stimulation (EFS), ACh and 5-hydroxytryptamine (5-HT) was not significantly altered in tracheal preparations from antigen immunized rabbits compared with littermate controls. Antigen challenge of immunized rabbits did not affect the release of ACh from isolated trachea following EFS, or the ability of oxotremorine to inhibit ACh release, Furthermore, antigen challenge of immunized rabbits failed to alter the contractile response to EFS or ACh, but reduced the contractile potency of 5-HT. These results demonstrate increased ACh release in tracheal preparations following immunization which had no functional consequence on airway smooth muscle responsiveness. Moreover, the increased release in ACh was not associated with an alteration in M-2-receptor function. Thus, antigen-induced bronchial hyperresponsiveness in the rabbit does not appear to depend upon M-2-receptor dysfunction. (C) 1999 Academic Press.