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Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation
- Source :
- Proceedings of the National Academy of Sciences of the United States. Nov 20, 2001, Vol. 98 Issue 24, p14114, 6 p.
- Publication Year :
- 2001
-
Abstract
- Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp[5.sup.-/-]) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp[5.sup.+/+] mice, Aqp[5.sup.-/-] mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp[5.sup.-/-] mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp[5.sup.-/-] mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.
Details
- ISSN :
- 00278424
- Volume :
- 98
- Issue :
- 24
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.80853001