title: Protease-activated receptor (Par)1 alters bioelectric properties of distal lung epithelia without compromising barrier function.
abstract: Proteinases contribute to the pathogenesis of various lung diseases, partly through activating cell surface receptors by limited proteolytic cleavage. The authors provide evidence that in primary cultures of distal lung epithelia, basolateral protease-activated receptor 1 activation rapidly reduces transepithelial resistance but does not alter paracellular permeability to small uncharged solutes. Changes in transepithelial resistance were partially blocked by ion transport inhibitors and were completely blocked by placing cells in low chloride buffer. In vivo studies did not reveal enhanced lung permeability in response to pulmonary or intravenous administration of protease-activated receptor 1 activators. This information is relevant as strategies to inhibit protease-activated receptor 1 signaling are considered in order to preserve lung epithelial barrier function.
authors.affiliation: Department of Medicine, The University of Toronto, Toronto, Ontario, Canada.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Moraes
authors.forename: Bijan
authors.initials: B
authors.lastname: Rafii
authors.forename: Frank
authors.initials: F
authors.lastname: Niessen
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Raiza
authors.initials: R
authors.lastname: Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Vachon
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Wolfram
authors.initials: W
authors.lastname: Ruf
authors.forename: Hugh
authors.initials: H
authors.lastname: O'Brodovich
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Downey
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D018118:Chloride Channels; D017097:Electric Impedance; D004848:Epithelium / Q000502:physiology*; D017136:Ion Transport; D008168:Lung / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D044463:Receptor, PAR-1