Document Detail

Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions.
MedLine Citation:
PMID:  16537379     Owner:  NLM     Status:  MEDLINE    
Aquaporin-5 (AQP5) is expressed in epithelia of lung, cornea, and various secretory glands, sites where extracellular osmolality is known to fluctuate. Hypertonic aquaporin (AQP) induction has been described, but little is known about the effects of a hypotonic environment on AQP abundance. We report that, when mouse lung epithelial cells were exposed to hypotonic medium, a dose-responsive decrease in AQP5 abundance was observed. Hypotonic reduction of AQP5 was blocked by ruthenium red, methanandamide, and miconazole, agents that inhibit the cation channel transient receptor potential vanilloid (TRPV) 4 present in lung epithelial cells. Several observations indicate that TRPV4 participates in hypotonic reduction of AQP5, including a requirement for extracellular calcium to achieve AQP5 reduction; an increase in intracellular calcium in mouse lung epithelial (MLE) cells after hypotonic stimulation; and reduction of AQP5 abundance after addition of the TRPV4 agonist 4alpha-Phorbol-12,13-didecanoate (4alpha-PDD). Similarly, addition of hypotonic PBS to mouse trachea in vivo decreased AQP5 within 1 h, an effect blocked by ruthenium red. To confirm a functional interaction, AQP5 was expressed in control or TRPV4-expressing human embryonic kidney (HEK) cells. Hypotonic reduction of AQP5 was observed only in the presence of TRPV4 and was blocked by ruthenium red. Combined with earlier studies, these observations indicate that AQP5 abundance is tightly regulated along a range of osmolalities and that AQP5 reduction by extracellular hypotonicity can be mediated by TRPV4. These findings have direct relevance to regulation of membrane water permeability and water homeostasis in epithelia of the lung and other organs.
Venkataramana K Sidhaye; Ali D Güler; Kelly S Schweitzer; Franco D'Alessio; Michael J Caterina; Landon S King
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-03-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-22     Completed Date:  2006-05-11     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4747-52     Citation Subset:  IM    
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
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MeSH Terms
Aquaporin 5 / metabolism*
Biological Transport
Calcium / metabolism
Cell Membrane / drug effects,  metabolism
Epithelial Cells / drug effects,  metabolism
Hypotonic Solutions / pharmacology
Lung / cytology,  drug effects,  metabolism*
Mice, Inbred C57BL
Osmotic Pressure
Phorbol Esters / pharmacology
Ruthenium Red / pharmacology
TRPV Cation Channels / agonists,  antagonists & inhibitors,  metabolism*
Trachea / cytology,  drug effects,  metabolism
Water / metabolism*
Grant Support
1R01 NS 051551-01/NS/NINDS NIH HHS; F32 HL 074515/HL/NHLBI NIH HHS; R01 HL 70217/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Aquaporin 5; 0/Hypotonic Solutions; 0/Phorbol Esters; 0/TRPV Cation Channels; 0/TRPV4 protein, human; 11103-72-3/Ruthenium Red; 70278-05-6/12-deoxyphorbol-13-decanoate; 7440-70-2/Calcium; 7732-18-5/Water

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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