Protease-activated receptor (Par)1 alters bioelectric properties of distal lung epithelia without compromising barrier function.
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.
Moraes
Theo J
TJ
Department of Medicine, The University of Toronto, Toronto, Ontario, Canada.
Rafii
Bijan
B
Niessen
Frank
F
Suzuki
Tomoko
T
Martin
Raiza
R
Vachon
Eric
E
Vogel
Wolfgang
W
Ruf
Wolfram
W
O'Brodovich
Hugh
H
Downey
Gregory P
GP
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*
D018118:Chloride Channels; D044463:Receptor, PAR-1