IN-VIVO QUANTIFICATION OF HUMAN PULMONARY BETA-ADRENOCEPTORS - EFFECTOF BETA-AGONIST THERAPY

In human subjects, chronic beta(2)-agonist dosing reduces mononuclear leukocyte (MNL) beta-adrenoceptor numbers. The aim of this study was t o investigate whether this downregulation also occurs in the lung. Sev en healthy male subjects were treated for 2 wk with oral (up to 16 mg/ d) and inhaled (up to 1.6 mg/d) albuterol (salbutamol in Europe). Pulm onary maximal beta-adrenoceptor binding capacity (Bmax) was determined in vivo using positron emission tomography (PET) and the beta-recepto r antagonist ligand, C-11-labeled CGP-12177, before and after the 2-wk chronic dosing. MNL Bmax was also measured, using a radioligand bindi ng assay and H-3-labeled CGP-12177. Bronchodilator responses to the be ta(2)-agonist were determined after each PET scan by measuring the cha nge in specific airway conductance (SGaw) after increasing doses of in haled albuterol. Pulmonary and MNL Bmax fell by 22% +/- 14% (p < 0.05) and 42% +/- 19% (p < 0.05) respectively. The changes in pulmonary and MNL Bmax were correlated (r = 0.9, p < 0.05). There was also a reduct ion in the bronchodilator response to inhaled albuterol. In a further six subjects, pulmonary and MNL Bmax did not change during an acute in fusion of albuterol (2 to 4 mu g/kg/h). The reduction in pulmonary bet a-adrenoceptor numbers after chronic albuterol dosing may be predictab le from the changes observed in circulating MNL cells.