Allergen challenge of passively sensitized human bronchi alters M2 and beta2 receptor function.
We investigated whether antigen challenge may alter M2 and beta2 receptor function in isolated passively sensitized human bronchi. Bronchial rings (2-4 mm internal 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 M2 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 beta2 receptor function by precontracting with carbachol 10(-6) M and adding cumulatively salbutamol (10(-9) M to 10(-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 force 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 M2 and beta2 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.
Song
P
P
Cattedra di Fisiopatologia Respiratoria, Dipartimento di Scienze Motorie e Riabilitative, Facoltà di Medicina e Chirurgia, Università di Genova, Italy.
Milanese
M
M
Crimi
E
E
Rehder
K
K
Brusasco
V
V
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D006801:Humans; D007114:Immunization; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D043585:Receptor, Muscarinic M2; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000485:Allergens; D001993:Bronchodilator Agents; D018721:Muscarinic Agonists; D043585:Receptor, Muscarinic M2; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D002217:Carbachol; D013806:Theophylline; D000242:Cyclic AMP; D000420:Albuterol