Article: article from journal or magazin.
Selected contribution: long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice.
Journal of Applied Physiology
Publication types: Journal Article
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.
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
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