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Originally published In Press as doi:10.1074/jbc.M008760200 on April 4, 2001

J. Biol. Chem., Vol. 276, Issue 26, 23413-23420, June 29, 2001
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Salivary Acinar Cells from Aquaporin 5-deficient Mice Have Decreased Membrane Water Permeability and Altered Cell Volume Regulation*

Carissa M. KraneDagger , James E. Melvin§, Ha-Van Nguyen§, Linda Richardson§, Jennifer E. TowneDagger , Thomas DoetschmanDagger , and Anil G. MenonDagger ||

From the Dagger  Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524 and the § Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

Aquaporins (AQPs) are channel proteins that regulate the movement of water through the plasma membrane of secretory and absorptive cells in response to osmotic gradients. In the salivary gland, AQP5 is the major aquaporin expressed on the apical membrane of acinar cells. Previous studies have shown that the volume of saliva secreted by AQP5-deficient mice is decreased, indicating a role for AQP5 in saliva secretion; however, the mechanism by which AQP5 regulates water transport in salivary acinar cells remains to be determined. Here we show that the decreased salivary flow rate and increased tonicity of the saliva secreted by Aqp5-/- mice in response to pilocarpine stimulation are not caused by changes in whole body fluid homeostasis, indicated by similar blood gas and electrolyte concentrations in urine and blood in wild-type and AQP5-deficient mice. In contrast, the water permeability in parotid and sublingual acinar cells isolated from Aqp5-/- mice is decreased significantly. Water permeability decreased by 65% in parotid and 77% in sublingual acinar cells from Aqp5-/- mice in response to hypertonicity-induced cell shrinkage and hypotonicity-induced cell swelling. These data show that AQP5 is the major pathway for regulating the water permeability in acinar cells, a critical property of the plasma membrane which determines the flow rate and ionic composition of secreted saliva.


* This work was supported in part by National Institutes of Health Grants RO1 DE138283 and ES06096 (to A. G. M.), RO1 DEO8921 (to J. E. M.), NHLBI, National Institutes of Health, Program of Excellence in Molecular Biology of Heart and Lung Grant HL61781 (to A. G. M.) and for new investigator support from this program (to C. M. K.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported in part by a predoctoral fellowship from the University of Cincinnati.

|| To whom correspondence should be addressed: Dept. of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 231 Bethesda Ave., 3110 MSB, P. O. Box 670524, Cincinnati, OH 45267-0524. Tel.: 513-558-5534; Fax: 513-558-1885; E-mail: Anil.Menon@UC.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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