Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation.
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 (Aqp5(-/-)) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5(+/+) mice, Aqp5(-/-) 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 Aqp5(-/-) mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5(-/-) 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.
Krane
C M
CM
Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA.
Fortner
C N
CN
Hand
A R
AR
McGraw
D W
DW
Lorenz
J N
JN
Wert
S E
SE
Towne
J E
JE
Paul
R J
RJ
Whitsett
J A
JA
Menon
A G
AG
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D051402:Aquaporin 5; D020346:Aquaporins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D005260:Female; D007537:Isometric Contraction; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009929:Organ Size; D011510:Proteolipids / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D020346:Aquaporins; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D008565:Membrane Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D007545:Isoproterenol; D000109:Acetylcholine