Allergen challenge of passively sensitized human bronchi alters M(2) and beta(2) receptor function

We investigated whether antigen challenge may alter M(2) and beta(2) receptor function in isolated passively sensitized human bronchi, Bronchial rings (2-4 mm infernal diameter) were obtained from 12 patients. Passive sensitization was induced by serum containing high IgE levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Rings from six patients were used to study M(2) receptor function by incubating with cumulatively increasing concentrations (10(-8) M to 10(-4) M) of pilocarpine and applying electric field stimulation (EFS) at 24 Hz. The rings from the other six patients were used to study beta(2) receptor function by precontracting with carbachol 10(-6) M and adding cumulatively salbutamol (10(-9) M to M(-4) M). Additional rings from these patients were used to determine whether dysfunction occurred distal to cAMP production by precontracting with carbachol 10(-6) M and adding cumulatively theophylline (10(-9) M to 10(-4) M). The attenuation of EFS-induced forte by pilocarpine and the relaxation of carbachol-precontracted rings by salbutamol were less in challenged than in control and sensitized rings. No difference between challenged, sensitized, and control rings was observed with theophylline, We conclude that allergen challenge in passively sensitized isolated human bronchial rings may result in M(2) and beta(2) receptor dysfunction without involving mechanisms distal to cAMP formation. it appears that products from inflammatory cells recruited from blood are not necessary for this receptor dysfunction.