In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats

Carlsson, Ola; Nielsen, S. B.; Zakaria, El Rasheid; Rippe, Bengt

doi:10.1152/ajpheart.1996.271.6.h2254

Cited by 72 publications

(86 citation statements)

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“…Water equilibration across the vasa recta may also play a critical role in avoiding the disruption of the osmotic gradient established by the countercurrent exchanger. It should also be mentioned that the demonstrated role of aquaporins, including AQP1 for peritoneal transport of water in experimental peritoneal dialysis (19), was also later confirmed in AQP1-deficient mice (259).…”

Section: A Aqp1mentioning

confidence: 95%

“…Functional studies were performed using isolated perfused descending vasa recta briefly fixed with glutaraldehyde. This fixation was performed to eliminate the cellular toxicity of mercurials, and it has been shown in collecting duct (124), toad urinary bladders (241), and peritoneum (19) that fixation at least partially maintains the osmotic water permeability. The fixed descending vasa recta displayed a marked sensitivity for mercurials on the transendothelial water permeability, confirming that AQP1 at this site may play a significant role for water transport.…”

Section: A Aqp1mentioning

confidence: 99%

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Aquaporins in the Kidney: From Molecules to Medicine

Nielsen

Frøkiær

Marples

et al. 2002

Physiological Reviews

1,119

1,022

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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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Section: A Aqp1mentioning

confidence: 95%

Section: A Aqp1mentioning

confidence: 99%

Aquaporins in the Kidney: From Molecules to Medicine

Nielsen

Frøkiær

Marples

et al. 2002

Physiological Reviews

1,119

1,022

View full text Add to dashboard Cite

show abstract

“…These large pores account for only 0.01% of the total population of capillary pores and transport across them occurs by hydrostatic pressure-driven unidirectional filtration from the plasma to the peritoneal cavity. In addition, the capillary wall has a high permeability to osmotic water transport through ultrasmall, water-only pores of radius ~2.5 Å present in the endothelial cell membrane (13,14).…”

Section: Structure Of the Peritoneal Membranementioning

confidence: 99%

“…Of interest is the location of the side chain of a cysteine residue (Cys189) in the pore, explaining why the water permeability mediated by AQP1 is inhibited by mercury compounds (23). The functional relevance of AQP1 for PD was first suggested by ex vivo inhibition of peritoneal water permeability by HgCl2 in a rat model (13). Studies conducted in the Aqp1 knock-out (KO) mice demonstrated that the osmotically-driven water transport across the peritoneal membrane was significantly decreased in Aqp1-/-mice, as compared with wild-type littermates (26).…”

Section: Aquaporin-1 Is the Ultrasmall Pore Of The Peritoneal Membranementioning

confidence: 99%

Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated. ABSTRACTPeritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a threepore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haplo-insufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.The development of peritoneal dialysis (PD) as a successful therapy for patients with end stage renal disease has been paralleled by the need to understand the transport mechanisms operating in the peritoneal membrane. Functional alterations in the dialysis capacity of the...

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“…Kinetic models of peritoneal dialysis postulate distinct classes of 'pores' that transport water and solutes to various extents, including an ultrasmall, 'water-only' pore. Early expression studies and measurements of mercurial inhibition of peritoneal water transport suggested that the water-only pore is AQP1 (44), which has been localized to capillary endothelia and mesangium near the peritoneal luminal surface.…”

Section: Role Of Aquaporins In Peritoneal Fluid Transportmentioning

confidence: 99%

Dissecting the Roles of Aquaporins in Renal Pathophysiology Using Transgenic Mice

Verkman

2008

Seminars in Nephrology

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Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1-4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2-4 impairs urinary concentrating ability by reduction of transcellular water permeability in collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration following renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics.

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In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats

Cited by 72 publications

References 0 publications

Aquaporins in the Kidney: From Molecules to Medicine

Aquaporins in the Kidney: From Molecules to Medicine

Water transport across the peritoneal membrane

Dissecting the Roles of Aquaporins in Renal Pathophysiology Using Transgenic Mice

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