Selected contribution: long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice.
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.
Sartori
C
C
Cardiovascular Research Institute, University of California, San Francisco, California 94143-0130, USA.
Fang
X
X
McGraw
D W
DW
Koch
P
P
Snider
M E
ME
Folkesson
H G
HG
Matthay
M A
MA
D000318:Adrenergic beta-Agonists / Q000097:blood / Q000494:pharmacology*; D000420:Albuterol / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009994:Osmolar Concentration; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D013726:Terbutaline; D000420:Albuterol