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cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells.

Identifieur interne : 001E08 ( Main/Exploration ); précédent : 001E07; suivant : 001E09

cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells.

Auteurs : Venkataramana Sidhaye [États-Unis] ; Jason D. Hoffert ; Landon S. King

Source :

RBID : pubmed:15536076

Descripteurs français

English descriptors

Abstract

Aquaporin-5 (AQP5) is present on the apical membrane of epithelial cells in various secretory glands as well as on the apical membrane of the airway epithelium, airway submucosal glands, and type 1 pneumocytes, where it can participate in respiratory tract water homeostasis. We examined the effects of cAMP on AQP5 distribution and abundance. When AQP5-expressing mouse lung epithelial cells were treated with cAMP or the beta-adrenergic agonist terbutaline, a biphasic AQP5 response was observed. Short term (minutes) exposure to cAMP produced internalization of AQP5 off of the membrane and a decrease in protein abundance. Both of these responses were blocked by inhibition of protein kinase A and the decrease in abundance was blocked by chloroquine, indicating lysosome-mediated degradation. Sustained cAMP exposure (hours) produced an increase in membrane localization and increased abundance; these effects were also blocked by protein kinase A inhibition. The beta-adrenergic agonist terbutaline produced changes in AQP5 abundance in mouse trachea and lung, consistent with our findings in cultured epithelial cells. Purified AQP5 protein was phosphorylated by protein kinase A but not protein kinase C or casein kinase II, and aquaporin-5 was phosphorylated in cultured cells after long term (but not short term) exposure to cAMP. These studies indicate that cAMP and beta-adrenergic agonists produce distinct short and long term effects on AQP5 distribution and abundance that may contribute to regulation of lung water homeostasis.

DOI: 10.1074/jbc.M411038200
PubMed: 15536076


Affiliations:


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Le document en format XML

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<term>Animals</term>
<term>Aquaporin 5</term>
<term>Aquaporins (metabolism)</term>
<term>Cyclic AMP (metabolism)</term>
<term>Epithelial Cells (cytology)</term>
<term>Epithelial Cells (drug effects)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Homeostasis (physiology)</term>
<term>Lung (cytology)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Mice</term>
<term>Terbutaline (pharmacology)</term>
<term>Trachea (cytology)</term>
<term>Water (metabolism)</term>
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<term>AMP cyclique (métabolisme)</term>
<term>Agonistes bêta-adrénergiques (pharmacologie)</term>
<term>Animaux</term>
<term>Aquaporine-5</term>
<term>Aquaporines (métabolisme)</term>
<term>Cellules épithéliales ()</term>
<term>Cellules épithéliales (cytologie)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Eau (métabolisme)</term>
<term>Homéostasie (physiologie)</term>
<term>Poumon (cytologie)</term>
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<term>Terbutaline (pharmacologie)</term>
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<div type="abstract" xml:lang="en">Aquaporin-5 (AQP5) is present on the apical membrane of epithelial cells in various secretory glands as well as on the apical membrane of the airway epithelium, airway submucosal glands, and type 1 pneumocytes, where it can participate in respiratory tract water homeostasis. We examined the effects of cAMP on AQP5 distribution and abundance. When AQP5-expressing mouse lung epithelial cells were treated with cAMP or the beta-adrenergic agonist terbutaline, a biphasic AQP5 response was observed. Short term (minutes) exposure to cAMP produced internalization of AQP5 off of the membrane and a decrease in protein abundance. Both of these responses were blocked by inhibition of protein kinase A and the decrease in abundance was blocked by chloroquine, indicating lysosome-mediated degradation. Sustained cAMP exposure (hours) produced an increase in membrane localization and increased abundance; these effects were also blocked by protein kinase A inhibition. The beta-adrenergic agonist terbutaline produced changes in AQP5 abundance in mouse trachea and lung, consistent with our findings in cultured epithelial cells. Purified AQP5 protein was phosphorylated by protein kinase A but not protein kinase C or casein kinase II, and aquaporin-5 was phosphorylated in cultured cells after long term (but not short term) exposure to cAMP. These studies indicate that cAMP and beta-adrenergic agonists produce distinct short and long term effects on AQP5 distribution and abundance that may contribute to regulation of lung water homeostasis.</div>
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