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REVIEW ARTICLE
Year : 2002  |  Volume : 19  |  Issue : 1  |  Page : 1-3
 

Aquaporins of the kidney: In health and disease states


Department of Nephrology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, India

Correspondence Address:
V Sivakumar
Department of Nephrology, SVIMS, Tirupati - 517 507
India
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Source of Support: None, Conflict of Interest: None


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   Abstract 

Aquaporins are a group of Tran membrane proteins, which function as molecular water channels. They were discovered by Agre and co-workers. Five Aquaporin pro­teins (AQPJ,2,3,4,6) are presently known to be expressed in the kidney with definite localization. Regarding three additional Aquaporins (AQP7, 8 and 10) the exact cellu­lar localization is not yet determined, but they are shown to be expressed at mRNA level in the kidney. The research on Aquaporins is providing molecular insight into the understanding of fundamental aspects of water balance in health and disease states.


Keywords: Aquaporins; Kidney; Health; Disease


How to cite this article:
Sivakumar V. Aquaporins of the kidney: In health and disease states. Indian J Urol 2002;19:1-3

How to cite this URL:
Sivakumar V. Aquaporins of the kidney: In health and disease states. Indian J Urol [serial online] 2002 [cited 2019 Dec 15];19:1-3. Available from: http://www.indianjurol.com/text.asp?2002/19/1/1/20283



   Introduction Top


The permeability of plasma membrane of mammalian cells is variable amongst tissues. Water crosses most of the cellular plasma membranes by simple diffusion. How­ever several biological membranes show large water trans­port capacity suggesting the involvement of some other mechanism in addition to simple diffusion and further re­search on this lines revealed the role of Aquaporins, the water channels, for the rapid and high degree of water permeability across endothelial and epithelial membranes with low energy expenditure. [1],[2],[3],[4],[5]

The research studies on amphibian physiology revealed the importance of water conservation in helping the ani­mal to survive dehydration, in terrestrial habitat. Antidiu­retic hormone (ADH) and Aquaporins have been found to be of special significance, in this process of terrestrial adaptation from amphibians to humans in maintaining medullary tonicity and renal concentrating mechanism to conserve water. The heterogeneity observed in various segments of nephron, in water handling, in the form of high water permeability in the proximal tubule and de­scending limb of Henle, very low water permeability in ascending limb of Henle and ADH regulated water permeability in the collecting duct are the adaptations that have occurred in the nephron in the evolutionary ladder from aquatic habitat to terrestrial habitat of the animal. [4],[5]


   Structure Top


Aquaporin is a tetramer, wherein four monomers are tightly packed. Each monomer is cylindrical in shape with a diameter of 30 Armstrongs. Each monomer has six membrane- spanning domains with five connecting loops­A,B,C,D and E. The B and E loops contain a structural motif Asn-Pro-Ala (Asparagine-Proline-Alanine) named as NPA box, which represents half of the vestibule or the channel. Thus when both NPA boxes meet between lipid bilayers, they form a single channel responsible for water permeability. The carboxy- and amino terminals of the Aquaporin molecule reside within the cell. The Aquaporins are classified into two groups, water selective channels (Orthodox Aquaporins) and Aquaglyceroproteins (chan­nels permeated by water, glycerol and other small mol­ecules) depending on permeability characters. [2],[3],[5],[6],[7]


   Distribution and Function Top


5 Aquaporins (AQP1, 2, 3, 4, 6) are presently known to be expressed at definite locations in the kidney and 3 ad­ditional Aquaporins (AQP7, 8 and 10) have been shown to be expressed at the mRNA level, but the cellular localization pattern is yet to be identified [Table - 1]. [2],[3],[5],[6],[7] The Xenopus oocyte has become an indispensable tool in Aquaporin research. Cloned RNA obtained by in vitro tran­scription of cloned DNA from the presumed source of Aquaporin is injected into the cytoplasm of the oocyte. Then the cloned RNA, by translation, synthesizes the par­ticular protein. When oocyte is placed in hypotonic me­dium, if the particular protein, synthesized by the oocyte, is an Aquaporin, it results in water movement into the oocyte and its swelling. The rate of swelling is measured by video microscopy. Thus the water permeating nature of a protein is identified with the help of oocyte technique in Aquaporin research. [5] Aquaporin 0 is the major intrinsic protein of the lens of the eye. Mutations of this gene re­sponsible for AQPO is known to induce cataract formation in mice. [4]


   AQP 1 Top


It is abundantly distributed in the apical and basolateral membrane of proximal tubule and descending thin limb, where it helps in entry and exit of water molecules and thus plays crucial role in water absorption in proximal nephron. Its presence in descending vasorecta helps in countercurrent exchange process of renal medulla. AQPI is considered as archetypal and was initially called as CHIP 28 (Channel-formin(T Integral Protein of 28kda). Critical role of AQPI in urinary concentration was recently stud­ied in transgenic mice with knockout of AQPI gene. They were polyuric, with reduced urinary concentrating capac­ity and 80%-90% reduction in osmotic water permeabil­ity, illustrating the important role of AQPI in water transport across these tubular segments. However, humans are phenotypically normal even when AQP1 is absent. In normal circumstances, even when AQPI is absent, pres­ence of AQP7, hypertonic medulla, paracellular water movement in descending limb of Henle, active sodium and chloride absorption in thick ascending limb of the Henle help in water movement across proximal nephron. [3],[5],[6],[7]


   AQP 2 Top


It is exclusively expressed in the principal cells of col­lecting duct. It is predominantly located in the apical plasma membrane and sub-apical vesicles and also in the basolateral plasma membrane in the inner medullary col­lecting duct. AQP2 is the predominant vasopressin-regu­lated water channel in the collecting duct. In the rat experimental studies, it is observed that administration of vasopressin caused fivefold rise in water permeability and redistribution of AQP2 to the apical membrane. Vasopressin acts through a surface V2 receptor, with the help of adenyl cyclase system. On stimulation by vasopressin, cytoplasmic vesicles containing AQP2 are targeted to cell surface by the help of vesicle targeting proteins Syntaxin­4 and Synaptobrevin-2. This process of redistribution of intracellular vesicles to the apical surface of principal cells is referred as the "membrane shuttle mechanism". In con­genital nephrogenic diabetes insipidus, AQP2 gene ab­normalities have been found to be playing significant role resulting in renal concentration abnormality and polyuria. In this entity, vasopressin secretion and vasopressin- me­diated V2 receptor stimulation pathways are intact. Lithium reduces AQP2 expression resulting in polyuria, when used in the treatment of patients of bipolar disorders. Similar findings of reduced AQP2 expression and polyuria were noted in chronic ureteric obstruction and release of ob­struction such as after prostatic surgery and in chronic hypokalemia-induced polyuria and in nocturnal enuresis. In patients of congestive cardiac failure, cirrhosis of liver, syndrome of inappropriate secretion of anti-diuretic hor­mone and in pregnancy, increased expression of AQP2 has been documented. This results in fluid logged state in these situations. [3],[7],[8],[9],[10],[11],[12],[13],[14]


   AQP 3 Top


It is selectively expressed in the basolateral plasma membrane of principal cells of collecting duct. Unlike AQPI and AQP2, AQP3 is permeable to glycerol and urea in addition to water. AQP3 has 33% identity to AQPI in structure. AQP3 deficiency has not been reported in humans. [3],[7],[8],[9],[10]


   AQP 4 Top


It is predominantly expressed in brain. It is also seen in basolateral membranes of collecting duct of principal cells in the inner medulla. This protein presumably provides the exit pore from these cells during vasopressin depend­ent water reabsorption. Disruption of the mouse AQP4 gene has been reported to result in a defect in renal con­centration. [8],[9],[10],[11]


   AQP 6 Top


It is reported to have extremely low inherent water per­meability. In rat kidney, this Aquaporin has been shown to reside in intracellular vesicles at three sites: within foot processes of glomerular podocytes, in subepithelial api­cal vesicles of proximal tubules and in alpha-intercalated cells of collecting duct. AQP6 is believed to play a role in renal acid secretion in addition to water permeability. [8],[9],[10],[11],[13]


   AQP 7 Top


It is localized at brush border of proximal straight tu­bules. In the absence of AQP1, AQP7 helps in water per­meation through proximal tubule in humans. [10],[11],[13]

Thus there is considerable evidence now, that Aquaporins play critical role in regulation of body water balance, osmo­sensing, and cell volume regulation.[7],[8] A growing number of Aquaporin family members and localization of many Aquaporins in the same organ suggest that they work co­operatively. [13]

 
   References Top

1.Inaho J, Harris Jr. HW. Molecular mechanisms for the regulation of water transport in amphibian epithelia by antidiuretic hormone. Kidney Int 1995: 48: 1088-1096.  Back to cited text no. 1    
2.Sasaki S, Fushimi K, lschibashi K et al. Water channels in the kid­ney collecting duct. Kidney Int 1995; 48: 1082-1087.  Back to cited text no. 2    
3.Knepper MA. Wade JB, Terres J et al. Renal Aquaporins. Kidney Int 1996; 49: 1712-1717.  Back to cited text no. 3    
4.Wintour EM. Water channels and urea transporters: Clinical and Experimental Pharmacology and Physiology 1997; 24: 1-9.  Back to cited text no. 4    
5.Angenita F. Lieburg V, Knoers NVAM et al. Discovery of Aqua­porins : a breakthrough in research on renal water transport. Pediatric Nephrology 1995: 9: 228-234.  Back to cited text no. 5    
6.Zeidel ML. Recent advances in water transport. Seminars in Neph­rology 1998: 18(2): 167-177.  Back to cited text no. 6    
7.Nielssen S, Fror J, Knepper MA. Renal Aquaporins : Key roles in water balance and water balance disorders. Current opinion in Ne­phrology and Hypertension 1998; 7: 509-516.  Back to cited text no. 7    
8.Kwon TH. Hager H, Nejsum LN et al. Physiology and Pathophysi­ology of renal Aquaporins. Seminars in Nephrology 2001: 21(3): 231-238.  Back to cited text no. 8    
9.Agre P. Aquaporin water channels in Kidney. J Am See Nephrol 2000; 11: 764-777.  Back to cited text no. 9    
10.Knepper MA. Nielsen S, Linchou C et al. Mechanisms of vaso­pressin action in the renal collecting duct. Seminars in Nephrology 1994: 14(4): 302-321.  Back to cited text no. 10    
11.Nielsen S. Agre P. The Aquaporin family of water channels in kid­ney. Kidney Int 1995; 48: 1057-1068.  Back to cited text no. 11    
12.Knepper MA, Verbalis JG, Nielsen S. Role of Aquaporins in water balance disorders. Current opinion in Nephrology and Hyperten­sion 1997: 6(4): 367-371.  Back to cited text no. 12    
13.Yamamoto T. Sasaki S. Aquaporins in the kidney: emerging new aspects. Kidney Int 1998; 54: 1041-1051.  Back to cited text no. 13    
14.Sivakumar V. Kishorebabu S. Renal Aquaporins. Indian Journal of Nephrology 1999: 9(2): 31-33.  Back to cited text no. 14    



 
 
    Tables

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    Abstract
    Introduction
    Structure
    Distribution and...
    AQP 1
    AQP 2
    AQP 3
    AQP 4
    AQP 6
    AQP 7
    References
    Article Tables

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