Selected contribution: long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice

J Appl Physiol (1985). 2002 Nov;93(5):1875-80. doi: 10.1152/japplphysiol.00275.2002.


Stimulation of active fluid transport with beta-adrenergic receptor (betaAR) agonists can accelerate the resolution of alveolar edema. However, chronic betaAR-agonist administration may cause betaAR desensitization and downregulation that may impair physiological responsiveness to betaAR-agonist stimulation. Therefore, we measured baseline and terbutaline- (10(-3) M) stimulated alveolar fluid clearance in mice that received subcutaneously (miniosmotic pumps) either saline or albuterol (2 mg. kg(-1). day(-1)) for 1, 3, or 6 days. Continuous albuterol administration increased plasma albuterol levels (10(-5) M), an effect that was associated with 1) a significant decrease in betaAR density and 2) attenuation, but not ablation, of maximal terbutaline-induced cAMP production. Forskolin-mediated cAMP-release was unaffected. Continuous albuterol infusion stimulated alveolar fluid clearance on day 1 but did not increase alveolar fluid clearance on days 3 and 6. However, terbutaline-stimulated alveolar fluid clearance in albuterol-treated mice was not reduced compared with saline-treated mice. Despite significant reductions in betaAR density and agonist-mediated cAMP production by long-term betaAR-agonist exposure, maximal betaAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / blood
  • Albuterol / pharmacology*
  • Animals
  • Body Fluids / metabolism*
  • Cyclic AMP / metabolism
  • Drug Synergism
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Osmolar Concentration
  • Pulmonary Alveoli / metabolism*
  • Receptors, Adrenergic, beta / metabolism
  • Terbutaline / pharmacology*
  • Time Factors


  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Cyclic AMP
  • Terbutaline
  • Albuterol