Kunzelmann, Karl and Sun, J. and Markovich, D. and Koenig, Jens and Muerle, Bettina and Mall, M. and Schreiber, Rainer (2005) Control of ion transport in mammalian airways by protease activated receptors type 2 (PAR-2). FASEB JOURNAL, 19 (6). 969-+. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
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 Ca2+, which activates basolateral SK4 K+ channels and luminal Ca2+-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BRONCHIAL EPITHELIAL-CELLS; CYSTIC-FIBROSIS MOUSE; GUINEA-PIG; CL-SECRETION; INFLAMMATION; EXPRESSION; MICE; INHIBITION; MODULATION; CHANNELS; airway epithelium; trypsin; tryptase |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 May 2021 09:09 |
| Last Modified: | 17 May 2021 09:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36300 |
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