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Water Channel Physiology and Pathophysiology Symposium: Introduction
Water Channel Physiology and Pathophysiology Symposium: Introduction JEFF M. SANDS, MD
T
his issue of The American Journal of the Medical Sciences contains a symposium on water channels (aquaporins). The four review articles are written by outstanding investigators from the United States and Europe. These papers address important recent advances in our understanding of the role of aquaporins in renal physiology and pathophysiology. The first aquaporin (AQP1) was cloned by Peter Agre's laboratory in 1992.1 Subsequently, three additional aquaporins were cloned and shown to play vital roles in water transport in the kidney: AQP2,2 AQP3,3-5 and AQP4. 6 ,7 AQP2 is the vasopressin-regulated water channel. Changes in AQP2 playa key role in clinical conditions in which water homeostasis is abnormal, and are reviewed by Drs. Fr0kirer, Marples, Knepper, and Nielsen. In addition, low-protein diets, which are frequently prescribed to slow the progression of chronic renal failure, result in down-regulation of AQP2. 8 ,9 Mutations in AQP2, or in the vasopressin type 2 receptor, present clinically as congenital nephrogenic diabetes insipidus, and are reviewed by Drs. Deen and Knoers. The ability to "knock out" a specific gene in mice is a powerful method for evaluating the function of a specific gene, especially when a cell expresses many similar proteins, as is the case for aquaporins. Dr. Verkman reviews some important recent insights which resulted from studies of AQP1 or AQP4 knock-out mice. The final article, by Drs. Baum and Harris, discusses recent insights into the coordinate regulation of AQP2 and divalent mineral ion metabolism. This coordinate regulation is mediated by the calcium-sensing receptor and could have important clinical application to the pathogenesis of nephrolithiasis. The articles in this symposium illustrate how important advances in basic science can be rapidly Dr. Sands is a Professor of Medicine in the Renal Division of the Department ofMedicine, Emory University School ofMedicine, Atlanta, Georgia. Correspondence: Jeff M. Sands, MD, Renal Division, Emory University, WMRB Room 338, 1639 Pierce Drive, NE, Atlanta, . GA 30322.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Jeff M. Sands, MD
translated into improvements in our understanding of the pathogenesis and genetics of human diseases. This new understanding is almost certain to lead to breakthroughs in treatment and emphasizes the vital link between research and advances in our ability to treat disease. References 1. Preston GM, Carroll TP, Guggino WB, Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science. 1992;256:385-7.
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Water Channel Symposium: Introduction
2. Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993;361:549-52. 3. Ishibashi K, Sasaki S, Fushimi K, Uchida S, Kuwahara M, Saito H, et al. Molecular cloning and expression of a member ofthe aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc N atl Acad Sci USA. 1994;91:6269-73. 4. Ma T, Frigeri A, Hasegawa H, Verkman AS. Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. J BioI Chern. 1994;269:21845-9. 5. Echevarria M, Windhager EE, Tate SS, Frindt G. Cloning and expression of AQP3, a water channel from the medullary collecting duct of rat kidney. Proc N atl Acad Sci USA. 1994;91:10997 -11001.
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6. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS. Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J BioI Chern. 1994; 269:5497 -5500. 7. Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P. Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci USA. 1994;91:13052-6. 8. Sands JM, Naruse M, Jacobs JD, Wilcox IN, Klein JD. Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. J Clin Invest. 1996; 97 :2807 -14. 9. Kishore BK, Terris J, Fernandez-Llama P, Knepper MA. Ultramicro-determination of vasopressin-regulated renal urea transporter protein in microdissected renal tubules. Am J Physiol. 1997;272:F531-F537.
November 1998 Volume 316 Number 5
T
his issue of The American Journal of the Medical Sciences contains a symposium on water channels (aquaporins). The four review articles are written by outstanding investigators from the United States and Europe. These papers address important recent advances in our understanding of the role of aquaporins in renal physiology and pathophysiology. The first aquaporin (AQP1) was cloned by Peter Agre's laboratory in 1992.1 Subsequently, three additional aquaporins were cloned and shown to play vital roles in water transport in the kidney: AQP2,2 AQP3,3-5 and AQP4. 6 ,7 AQP2 is the vasopressin-regulated water channel. Changes in AQP2 playa key role in clinical conditions in which water homeostasis is abnormal, and are reviewed by Drs. Fr0kirer, Marples, Knepper, and Nielsen. In addition, low-protein diets, which are frequently prescribed to slow the progression of chronic renal failure, result in down-regulation of AQP2. 8 ,9 Mutations in AQP2, or in the vasopressin type 2 receptor, present clinically as congenital nephrogenic diabetes insipidus, and are reviewed by Drs. Deen and Knoers. The ability to "knock out" a specific gene in mice is a powerful method for evaluating the function of a specific gene, especially when a cell expresses many similar proteins, as is the case for aquaporins. Dr. Verkman reviews some important recent insights which resulted from studies of AQP1 or AQP4 knock-out mice. The final article, by Drs. Baum and Harris, discusses recent insights into the coordinate regulation of AQP2 and divalent mineral ion metabolism. This coordinate regulation is mediated by the calcium-sensing receptor and could have important clinical application to the pathogenesis of nephrolithiasis. The articles in this symposium illustrate how important advances in basic science can be rapidly Dr. Sands is a Professor of Medicine in the Renal Division of the Department ofMedicine, Emory University School ofMedicine, Atlanta, Georgia. Correspondence: Jeff M. Sands, MD, Renal Division, Emory University, WMRB Room 338, 1639 Pierce Drive, NE, Atlanta, . GA 30322.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Jeff M. Sands, MD
translated into improvements in our understanding of the pathogenesis and genetics of human diseases. This new understanding is almost certain to lead to breakthroughs in treatment and emphasizes the vital link between research and advances in our ability to treat disease. References 1. Preston GM, Carroll TP, Guggino WB, Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science. 1992;256:385-7.
289
Water Channel Symposium: Introduction
2. Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993;361:549-52. 3. Ishibashi K, Sasaki S, Fushimi K, Uchida S, Kuwahara M, Saito H, et al. Molecular cloning and expression of a member ofthe aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc N atl Acad Sci USA. 1994;91:6269-73. 4. Ma T, Frigeri A, Hasegawa H, Verkman AS. Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. J BioI Chern. 1994;269:21845-9. 5. Echevarria M, Windhager EE, Tate SS, Frindt G. Cloning and expression of AQP3, a water channel from the medullary collecting duct of rat kidney. Proc N atl Acad Sci USA. 1994;91:10997 -11001.
290
6. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS. Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J BioI Chern. 1994; 269:5497 -5500. 7. Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P. Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci USA. 1994;91:13052-6. 8. Sands JM, Naruse M, Jacobs JD, Wilcox IN, Klein JD. Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. J Clin Invest. 1996; 97 :2807 -14. 9. Kishore BK, Terris J, Fernandez-Llama P, Knepper MA. Ultramicro-determination of vasopressin-regulated renal urea transporter protein in microdissected renal tubules. Am J Physiol. 1997;272:F531-F537.
November 1998 Volume 316 Number 5