Airway smooth muscle receptor-mediated responsiveness and receptor characteristics for airway tissue from non-asthmatic and asthmatic patients, and guinea pigs with airway responsiveness, were investigated for airway preparations using drug concentration-response relationships and radiolabelled ligand binding studies. Between—patient variability was approximately SSO-fold greater than within-patient variability for B-adrenoceptor-mediated responsiveness of human airway tissue. Alteration in B-adrenoceptor characteristics (Kd and Bmax) could not account for the marked between-patient variability demonstrated for B-adrenoceptor mediated responsiveness. Exposure of human airway tissue in vivo with preoperative Bz-adrenoceptor agonist medication did not influence B-adrenoceptor-mediated responsiveness, however in vitro exposure of airway tissue to B-adrenoceptor agonist did reduce G-adrenoceptor-mediated responsiveness. This suggests, that in vivo concentrations reached for Bz-adrenoceptor agonist medication were not great enough to induce an alteration in B-adrenoceptor-mediated function. Chronic administration of B-adrenoceptor antagonist medication of patients and rats reduced B-adrenoceptor-mediated responsiveness of airway tissue in vivo. The B-adrenoceptor-mediated responsiveness of peripheral airway tissue from spontaneously hypertensive rats was similar to that for tissue from normotensive animals. Evidence suggests therefore that the reduced 8--adrenoceptor-mediated responsiveness is not due to the hypertension but to the accumulation of the 13--adrenoceptor antagonist in the peripheral airway tissue. Airway smooth muscle from asthmatic patients demonstrated similar relaxation responsiveness to tissue from non-asthmatics and reduced responsiveness to contractile agonists. These results suggest that airway hyperresponsiveness in vivo is regulated by factors other than smooth muscle characteristics. Relaxation responsiveness of airway smooth muscle from asthmatic patients was similar to that in non-asthmatic patients, however contractile responsiveness was reduced. Alteration of muscarinic cholinoceptor responsiveness, suggesting that alteration in muscarinic-mediated responsiveness is distal to the muscarinic cholinoceptors. B-Adrenoceptor characteristics remained unchanged. It is concluded that airway hyperresponsiveness in vivo is not represented by parallel changes in receptor-mediated tissue responsiveness, suggesting that neural and/or humoral influences may influence airway control.
