Albuterol modulates its own transepithelial flux via changes in paracellular permeability

Hoshang J. Unwalla, Gabor Horvath, Felix D. Roth, Gregory E. Conner, Matthias Salathe

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Although inhaled bronchodilators are commonly used in the treatment of airway disease to dilate airway smooth muscle, little is known regarding the mechanisms that regulate albuterol movement across the epithelium to reach its target, the airway smooth muscle. Because the rate of onset depends on the transepithelial transport of albuterol, to determine the mechanisms that regulate the transepithelial movement of albuterol is essential. Human bronchial epithelial cells, fully redifferentiated in culture at the air-liquid interface, were used to study the cellular uptake and total transepithelial flux of 3H-albuterol from the apical to the basolateral surfaces. 3H-mannitol and transepithelial electrical resistance were used to quantify changes in paracellular permeability. The majority of albuterol flux across the epithelium occurred via the paracellular route. The cellular uptake of albuterol was found to be saturable, whereas transepithelial flux was not. Cellular uptake could be inhibited by the amino acids lysine and histidine, with no effect on net transepithelial flux. Transepithelial flux was altered by maneuvers that collapsed or disrupted intercellular junctions. Acidification, usually seen in exacerbations of airway disease, decreased albuterol flux. In addition, albuterol increased its own paracellular permeability. The ability of albuterol to modulate paracellular permeability was blocked by the β 2-adrenergic receptor-selective antagonist ICI 118551. Albuterol mainly crosses the epithelium via the paracellular pathway, but has the ability tomodulate its own permeability through changes in the leakiness of tight junctions, which is modulated through the signaling of the β 2-adrenergic receptor.

Original languageEnglish (US)
Pages (from-to)551-558
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • β -adrenergic receptor signaling
  • Airway epithelial permeability modulation
  • Albuterol
  • Tight junctions
  • Transepithelial flux

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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