Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells.
A cytoprotective role for protease-activated receptor-2 (PAR2) has been suggested in a number of systems including the airway, and to this end, we have studied the role that PARs play in the regulation of airway ion transport, using cultures of normal human bronchial epithelial cells. PAR2 activators, added to the basolateral membrane, caused a transient, Ca2+-dependent increase in short-circuit current (I(sc)), followed by a sustained inhibition of amiloride-sensitive I(sc). These phases corresponded with a transient increase in intracellular Ca2+ concentration and then a transient increase, followed by decrease, in basolateral K+ permeability. After PAR2 activation and the addition of amiloride, the forskolin-stimulated increase in I(sc) was also attenuated. By contrast, PAR2 activators added to the apical surface of the epithelia or PAR1 activators added to both the apical and basolateral surfaces were without effect. PAR2 may, therefore, play a role in the airway, regulating Na+ absorption and anion secretion, processes that are central to the control of airway surface liquid volume and composition.
Danahay
H
H
Novartis Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom. henry.danahay@pharma.novartis.com
Withey
L
L
Poll
C T
CT
van de Graaf
S F
SF
Bridges
R J
RJ
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001980:Bronchi / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D006490:Hemostatics; D009842:Oligopeptides; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D015222:Sodium Channels; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D012964:Sodium; D014357:Trypsin; D013917:Thrombin; D002118:Calcium