Effects of beta-agonists on airway epithelial cells.
beta-Adrenergic receptor (betaAR) agonists exert a variety of effects on airway epithelial cells. Among their best known actions is their ability to increase ciliary beat frequency, mediated by cyclic adenosine monophosphate (cAMP) production, stimulation of protein kinase A (PKA), and phosphorylation of an outer dynein arm light chain. Submucosal glands express betaARs, and beta-agonists may stimulate secretion of mucus from airways, although human data are controversial. beta-Agonists may also affect ion transport across epithelial cells by opening apical ion channels such as the cystic fibrosis transmembrane regulator. This effect, likely to occur in submucosal glands, can influence water fluxes across the airway epithelium and may have profound influences on mucus hydration. betaAR activation can increase intracellular calcium in some ciliated cells, thereby stimulating ciliary beating and possibly influencing transepithelial ion transport. betaAR-mediated activation of cAMP-dependent protein kinase accelerates epithelial cell migration, thereby enhancing epithelial wound repair. beta-Agonists reduce the ultrastructural damage seen with infection and potentiate secretion of certain cytokines from epithelial cells while inhibiting secretion of others. Finally, beta-agonists may have effects on airway epithelial cells that are mediated through betaARs but do not require cAMP production. The signaling mechanisms of some beta-agonist effects are not well understood but are important to our understanding of airway epithelial cell growth, differentiation, and function.
Salathe
Matthias
M
Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, FL 33136, USA.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases