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Physiological Reviews, Vol. 82, No. 1, January 2002, pp. 205-244; 10.1152/physrev.00024.2001.
Copyright ©2002 by the American Physiological Society
The Water and Salt Research Center, Institute of Anatomy, and Institute of Experimental Clinical Research, University of Aarhus, Aarhus, Denmark; University of Leeds, Leeds, United Kingdom; Dongguk University, Kyungju, Korea; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore; and National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
Nielsen, Søren,
Jørgen Frøkiær,
David Marples,
Tae-Hwan Kwon,
Peter Agre, and
Mark A. Knepper.
Aquaporins in the Kidney: From Molecules to Medicine. Physiol. Rev. 82: 205-244, 2002.
The discovery of aquaporin-1 (AQP1)
answered the long-standing biophysical question of how water
specifically crosses biological membranes. In the kidney, at least
seven aquaporins are expressed at distinct sites. AQP1 is extremely
abundant in the proximal tubule and descending thin limb and is
essential for urinary concentration. AQP2 is exclusively expressed in
the principal cells of the connecting tubule and collecting duct and is
the predominant vasopressin-regulated water channel. AQP3 and AQP4
are both present in the basolateral plasma membrane of collecting duct
principal cells and represent exit pathways for water reabsorbed
apically via AQP2. Studies in patients and transgenic mice have
demonstrated that both AQP2 and AQP3 are essential for urinary
concentration. Three additional aquaporins are present in the kidney.
AQP6 is present in intracellular vesicles in collecting duct
intercalated cells, and AQP8 is present intracellularly at low
abundance in proximal tubules and collecting duct principal cells, but
the physiological function of these two channels remains undefined.
AQP7 is abundant in the brush border of proximal tubule cells and is
likely to be involved in proximal tubule water reabsorption. Body water
balance is tightly regulated by vasopressin, and multiple studies now
have underscored the essential roles of AQP2 in this. Vasopressin
regulates acutely the water permeability of the kidney collecting duct
by trafficking of AQP2 from intracellular vesicles to the apical plasma
membrane. The long-term adaptational changes in body water balance
are controlled in part by regulated changes in AQP2 and AQP3 expression
levels. Lack of functional AQP2 is seen in primary forms of diabetes
insipidus, and reduced expression and targeting are seen in several
diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as
acute and chronic renal failure. In contrast, in conditions with water
retention such as severe congestive heart failure, pregnancy, and
syndrome of inappropriate antidiuretic hormone secretion, both
AQP2 expression levels and apical plasma membrane targetting are
increased, suggesting a role for AQP2 in the development of water
retention. Continued analysis of the aquaporins is providing detailed
molecular insight into the fundamental physiology and pathophysiology
of water balance and water balance disorders.
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S. M. Saparov, K. Liu, P. Agre, and P. Pohl Fast and Selective Ammonia Transport by Aquaporin-8 J. Biol. Chem., February 23, 2007; 282(8): 5296 - 5301. [Abstract] [Full Text] [PDF]
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C. R. J. Kennedy, H. Xiong, S. Rahal, J. Vanderluit, R. S. Slack, Y. Zhang, Y. Guan, M. D. Breyer, and R. L. Hebert Urine concentrating defect in prostaglandin EP1-deficient mice Am J Physiol Renal Physiol, February 1, 2007; 292(2): F868 - F875. [Abstract] [Full Text] [PDF]
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S. O. Topcu, M. Pedersen, R. Norregaard, G. Wang, M. Knepper, J. C. Djurhuus, S. Nielsen, T. M. Jorgensen, and J. Frokiaer Candesartan prevents long-term impairment of renal function in response to neonatal partial unilateral ureteral obstruction Am J Physiol Renal Physiol, February 1, 2007; 292(2): F736 - F748. [Abstract] [Full Text] [PDF]
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H. Dimke, A. Flyvbjerg, S. Bourgeois, K. Thomsen, J. Frokiaer, P. Houillier, S. Nielsen, and S. Frische Acute growth hormone administration induces antidiuretic and antinatriuretic effects and increases phosphorylation of NKCC2 Am J Physiol Renal Physiol, February 1, 2007; 292(2): F723 - F735. [Abstract] [Full Text] [PDF]
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G. Nishimoto, G. Sasaki, E. Yaoita, M. Nameta, H. Li, K. Furuse, H. Fujinaka, Y. Yoshida, A. Mitsudome, and T. Yamamoto Molecular characterization of water-selective AQP (EbAQP4) in hagfish: insight into ancestral origin of AQP4 Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R644 - R651. [Abstract] [Full Text] [PDF]
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Y.-J. Lee, I.-K. Song, K.-J. Jang, J. Nielsen, J. Frokiaer, S. Nielsen, and T.-H. Kwon Increased AQP2 targeting in primary cultured IMCD cells in response to angiotensin II through AT1 receptor Am J Physiol Renal Physiol, January 1, 2007; 292(1): F340 - F350. [Abstract] [Full Text] [PDF]
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 N. Makhanova, M. L.S. Sequeira-Lopez, R. A. Gomez, H.-S. Kim, and O. Smithies Disturbed Homeostasis in Sodium-Restricted Mice Heterozygous and Homozygous for Aldosterone Synthase Gene Disruption Hypertension, December 1, 2006; 48(6): 1151 - 1159. [Abstract] [Full Text] [PDF]
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 M.-J. Yu, T. Pisitkun, G. Wang, R.-F. Shen, and M. A. Knepper LC-MS/MS Analysis of Apical and Basolateral Plasma Membranes of Rat Renal Collecting Duct Cells Mol. Cell. Proteomics, November 1, 2006; 5(11): 2131 - 2145. [Abstract] [Full Text] [PDF]
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J. D. Klein, B. P. Murrell, S. Tucker, Y.-H. Kim, and J. M. Sands Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension Am J Physiol Renal Physiol, November 1, 2006; 291(5): F952 - F959. [Abstract] [Full Text] [PDF]
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M. J. Page and E. Di Cera Role of na+ and k+ in enzyme function. Physiol Rev, October 1, 2006; 86(4): 1049 - 1092. [Abstract] [Full Text] [PDF]
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 C. Chassin, J.-M. Goujon, S. Darche, L. du Merle, M. Bens, F. Cluzeaud, C. Werts, E. Ogier-Denis, C. Le Bouguenec, D. Buzoni-Gatel, et al. Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways J. Immunol., October 1, 2006; 177(7): 4773 - 4784. [Abstract] [Full Text] [PDF]
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K.-P. Yip Epac-mediated Ca2+ mobilization and exocytosis in inner medullary collecting duct Am J Physiol Renal Physiol, October 1, 2006; 291(4): F882 - F890. [Abstract] [Full Text] [PDF]
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J. D. Klein, O. Frohlich, M. A. Blount, C. F. Martin, T. D. Smith, and J. M. Sands Vasopressin Increases Plasma Membrane Accumulation of Urea Transporter UT-A1 in Rat Inner Medullary Collecting Ducts J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2680 - 2686. [Abstract] [Full Text] [PDF]
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J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol, August 1, 2006; 291(2): F257 - F270. [Abstract] [Full Text] [PDF]
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D. Zhao, L. Bankir, L. Qian, D. Yang, and B. Yang Urea and urine concentrating ability in mice lacking AQP1 and AQP3 Am J Physiol Renal Physiol, August 1, 2006; 291(2): F429 - F438. [Abstract] [Full Text] [PDF]
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R. W. Schrier Body Water Homeostasis: Clinical Disorders of Urinary Dilution and Concentration J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1820 - 1832. [Full Text] [PDF]
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L. M. Russo, M. McKee, and D. Brown Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney Am J Physiol Renal Physiol, July 1, 2006; 291(1): F246 - F253. [Abstract] [Full Text] [PDF]
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M. Herrera, N. J. Hong, and J. L. Garvin Aquaporin-1 Transports NO Across Cell Membranes Hypertension, July 1, 2006; 48(1): 157 - 164. [Abstract] [Full Text] [PDF]
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 J. L. Gooch, R. L. Guler, J. L. Barnes, and J. J. Toro Loss of calcineurin A{alpha} results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus J. Cell Sci., June 15, 2006; 119(12): 2468 - 2476. [Abstract] [Full Text] [PDF]
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U. Hasler, U. S. Jeon, J. A. Kim, D. Mordasini, H. M. Kwon, E. Feraille, and P.-Y. Martin Tonicity-Responsive Enhancer Binding Protein Is an Essential Regulator of Aquaporin-2 Expression in Renal Collecting Duct Principal Cells J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1521 - 1531. [Abstract] [Full Text] [PDF]
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C. Li, W. Wang, S. N. Summer, M. A. Cadnapaphornchai, S. Falk, F. Umenishi, and R. W. Schrier Hyperosmolality In Vivo Upregulates Aquaporin 2 Water Channel and Na-K-2Cl Co-Transporter in Brattleboro Rats J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1657 - 1664. [Abstract] [Full Text] [PDF]
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F. J. M. Detmers, B. L. de Groot, E. M. Muller, A. Hinton, I. B. M. Konings, M. Sze, S. L. Flitsch, H. Grubmuller, and P. M. T. Deen Quaternary Ammonium Compounds as Water Channel Blockers: SPECIFICITY, POTENCY, AND SITE OF ACTION J. Biol. Chem., May 19, 2006; 281(20): 14207 - 14214. [Abstract] [Full Text] [PDF]
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P. Chen, J. P. Guzman, P. K. K. Leong, L. E. Yang, A. Perianayagam, E. Babilonia, J. S. Ho, J. H. Youn, W. H. Wang, and A. A. McDonough Modest dietary K+ restriction provokes insulin resistance of cellular K+ uptake and phosphorylation of renal outer medulla K+ channel without fall in plasma K+ concentration Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1355 - C1363. [Abstract] [Full Text] [PDF]
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M. Goel, W. G. Sinkins, C.-D. Zuo, M. Estacion, and W. P. Schilling Identification and localization of TRPC channels in the rat kidney Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1241 - F1252. [Abstract] [Full Text] [PDF]
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W. Wang, C. Li, S. N. Summer, S. Falk, M. A. Cadnapaphornchai, Y.-C. Chen, and R. W. Schrier Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1135 - F1142. [Abstract] [Full Text] [PDF]
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T. Pisitkun, J. Bieniek, D. Tchapyjnikov, G. Wang, W. W. Wu, R.-F. Shen, and M. A. Knepper High-throughput identification of IMCD proteins using LC-MS/MS Physiol Genomics, April 13, 2006; 25(2): 263 - 276. [Abstract] [Full Text] [PDF]
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A. Rojek, E.-M. Fuchtbauer, T.-H. Kwon, J. Frokiaer, and S. Nielsen Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice PNAS, April 11, 2006; 103(15): 6037 - 6042. [Abstract] [Full Text] [PDF]
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Y. Li, S. Shaw, E.-J. Kamsteeg, A. Vandewalle, and P. M.T. Deen Development of Lithium-Induced Nephrogenic Diabetes Insipidus Is Dissociated from Adenylyl Cyclase Activity J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1063 - 1072. [Abstract] [Full Text] [PDF]
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P. A. Ortiz cAMP increases surface expression of NKCC2 in rat thick ascending limbs: role of VAMP Am J Physiol Renal Physiol, March 1, 2006; 290(3): F608 - F616. [Abstract] [Full Text] [PDF]
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 J. M. Sands and D. G. Bichet Nephrogenic Diabetes Insipidus Ann Intern Med, February 7, 2006; 144(3): 186 - 194. [Full Text] [PDF]
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 M. J. Daniels, M. R. Wood, and M. Yeager In Vivo Functional Assay of a Recombinant Aquaporin in Pichia pastoris Appl. Envir. Microbiol., February 1, 2006; 72(2): 1507 - 1514. [Abstract] [Full Text] [PDF]
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