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Control of ion transport in mammalian airways by protease activated receptors type 2 (PAR‐2)
Author(s) -
Kunzelmann Karl,
Sun Jane,
Markovich Daniel,
König Jens,
Mürle Bettina,
Mall Marcus,
Schreiber Rainer
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2469fje
Subject(s) - stimulation , receptor , chemistry , amiloride , tryptase , respiratory epithelium , secretion , microbiology and biotechnology , proteases , protease activated receptor , medicine , immunology , biology , endocrinology , mast cell , biochemistry , respiratory system , sodium , enzyme , organic chemistry , thrombin , platelet
Protease‐activated receptors (PARs) are widely distributed in human airways. They couple to G‐proteins and are activated after proteolytic cleavage of the N terminus of the receptor. Evidence is growing that PAR subtype 2 plays a pivotal role in inflammatory airway diseases, such as allergic asthma or bronchitis. However, nothing is known about the effects of PAR‐2 on electrolyte transport in the native airways. PAR‐2 is expressed in airway epithelial cells, where they are activated by mast cell tryptase, neutrophil proteinase 3, or trypsin. Recent studies produced conflicting results about the functional consequence of PAR‐2 stimulation. Here we report that stimulation of PAR‐2 receptors in mouse and human airways leads to a change in electrolyte transport and a shift from absorption to secretion. Although PAR‐2 appears to be expressed on both sides of the epithelium, only basolateral stimulation results in inhibition of amiloride sensitive Na + conductance and stimulation of both luminal Cl ‐ channels and basolateral K + channels. The present data indicate that these changes occur through activation of phospholipase C and increase in intracellular Ca 2+ , which activates basolateral SK4 K + channels and luminal Ca 2+ ‐dependent Cl ‐ channels. In addition, the present data suggest a PAR‐2 mediated release of prostaglandin E2, which may contribute to the secretory response. In conclusion, these results provide further evidence for a role of PAR‐2 in inflammatory airway disease: stimulation of these receptors may cause accumulation of airway surface liquid, which, however, may help to flush noxious stimuli away from the affected airways.