Effect of sensitization and aerosol antigen challenge in guinea-pigs--studies of airway receptor function and characteristics

Immunological sensitization of guinea-pigs and subsequent antigen inhalation challenge has provided an animal model which has several features in common with human asthma. Impairment of beta-adrenoceptor-mediated function and mechanisms have been postulated to contribute to the hyperreactivity to contractile agonists demonstrated in vivo and in vitro in these animals. Functional and receptor radioligand binding studies were carried out on airway tissue from: non-sensitized; sensitized; sensitized saline challenged; sensitized antigen challenged guinea-pigs. Sensitization did not alter responsiveness of airway tissue to carbachol, although subsequent antigen challenge did increase carbachol sensitivity of peripheral airway tissue six-fold. Neither sensitization itself nor subsequent antigen challenge altered binding characteristics of the muscarinic cholinoceptor ligand [3H]quinuclidinyl benzilate ([3H]QNB) to peripheral airway tissue, suggesting that mechanisms responsible for increases in carbachol sensitivity are distal to these receptors. Relaxation of airway preparations to isoprenaline was not altered by sensitization or further antigen challenge of the animals. However, sensitization significantly reduced affinity but not the total number of binding sites in peripheral airway tissue for the beta-adrenoceptor ligand [3H]dihydroalprenolol ([3H]DHA). Antigen challenge of the animals did not further alter beta-adrenoceptor ligand binding characteristics. These results suggest that airway hyperreactivity in this model is not a function of alteration in receptor characteristics, or impairment of relaxation mechanisms.