In vivo quantification of human pulmonary beta-adrenoceptors: effect of beta-agonist therapy

Am J Respir Crit Care Med. 1996 Nov;154(5):1277-83. doi: 10.1164/ajrccm.154.5.8912736.


In human subjects, chronic beta2-agonist dosing reduces mononuclear leukocyte (MNL) beta-adrenoceptor numbers. The aim of this study was to investigate whether this downregulation also occurs in the lung. Seven 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). Pulmonary maximal beta-adrenoceptor binding capacity (Bmax) was determined in vivo using positron emission tomography (PET) and the beta-receptor antagonist ligand, 11C-labeled CGP-12177, before and after the 2-wk chronic dosing. MNL Bmax was also measured, using a radioligand binding assay and 3H-labeled CGP-12177. Bronchodilator responses to the beta2-agonist were determined after each PET scan by measuring the change in specific airway conductance (SGaw) after increasing doses of inhaled 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 reduction in the bronchodilator response to inhaled albuterol. In a further six subjects, pulmonary and MNL Bmax did not change during an acute infusion of albuterol (2 to 4 microg/kg/h). The reduction in pulmonary beta-adrenoceptor numbers after chronic albuterol dosing may be predictable from the changes observed in circulating MNL cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / blood
  • Albuterol / pharmacology*
  • Catecholamines / blood
  • Down-Regulation / drug effects
  • Humans
  • Infusions, Intravenous
  • Lung / drug effects*
  • Male
  • Monocytes / drug effects
  • Propanolamines / pharmacology*
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / metabolism
  • Reproducibility of Results
  • Tomography, Emission-Computed


  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Catecholamines
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Albuterol
  • CGP 12177