Acetazolamide inhibits osmotic water permeability by interaction with aquaporin-1

Gao, Junwei; Wang, Xiaohua; Chang, Yongjie; Zhang, Jianzhao; Song, Qianliu; Yu, Huidong; Li, Xuejun

doi:10.1016/j.ab.2006.01.003

Cited by 88 publications

(74 citation statements)

References 30 publications

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“…34,35) To evaluate the urinary osmotic pressure in the collecting tubules, where final urine volume was determined, the mRNA expression levels of the osmoregulatory genes (SMIT and TauT) and transporters related to osmotic pressure were measured.…”

Section: Discussionmentioning

confidence: 99%

Increases in the Expression Levels of Aquaporin-2 and Aquaporin-3 in the Renal Collecting Tubules Alleviate Dehydration Associated with Polyuria in Diabetes Mellitus

Satake

Ikarashi

Kagami

et al. 2010

Biological & Pharmaceutical Bulletin

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Aquaporins (AQPs) are water channels found widely in bacteria, plants, animals, and humans. There are presently 13 known types of aquaporins in humans (AQP0 to AQP12), which are expressed in various organs. 1) In the kidney, several members of the AQP family are expressed, which are responsible for regulating water volume in the body. Especially in the renal collecting duct, AQP2, which is expressed on the luminal membranes of principal cells, and AQP3 and AQP4, which are expressed on the basolateral membranes of principal cells, are involved in urine concentration by inducing the re-absorption of water from the luminal side to the basolateral side.2) The capacity for water re-absorption in the renal collecting duct is thought to determine urine volume. Because either protein mutations or a decreased expression of AQP2 is found in patients with nephrogenic diabetes insipidus who present with marked polyuria, AQP2 is considered to play the most important role in water re-absorption in the renal collecting duct. 3,4) Enhanced expression of renal AQP2 has been reported when polyuria occurs in streptozotocin (STZ)-induced type I diabetes model mice. 5,6) In addition, we previously found that the level of renal AQP2 expression increases along with the pathological progression of type II diabetes mellitus using KKAy mice, the animal model of type II diabetes. 7) Although this increased AQP2 expression in the kidneys has been regarded as a possible compensatory mechanism to alleviate dehydration in polyuria, the physiological significance of the increase in renal AQP2 expression in diabetes remains unknown. Recently, a method to generate a mouse model of nephrogenic diabetes insipidus by administering lithium carbonate (Li 2 CO 3 ) was reported. 8,9) Almost all of the Li 2 CO 3 absorbed into the body is eliminated unchanged via glomerular filtration. Lithium is incorporated into principal cells of the collecting tubules via epithelial sodium channels that are dominantly expressed on the collecting tubules.10) The incorporated lithium decreases cAMP by suppressing the activity of adenylate cyclase (AC), resulting in the inhibition of pathways for both AQP2 and AQP3 transcription and membrane transfer. 8,9,11) Using Li 2 CO 3 , we constructed an experimental system to decrease only the expression levels of AQPs, with no change in urinary osmotic pressure, to investigate the relationship between urine volume and the expression levels of AQPs. In this study, we developed this experimental system by administering Li 2 CO 3 to STZ-induced type I diabetes model mice. MATERIALS AND METHODSMaterials 2-Mercaptoethanol, bromophenol blue, Folin and Ciocalteu's phenol reagent, polyoxyethylene (20) sorbitan monolaurate (Tween 20), sodium dodecyl sulphate (SDS), and 2-amino-2-hydroxymethyl-1,3-propanediol (Tris) were purchased from Wako Pure Chemical Industries, Ltd. (Tokyo, Japan). Anti-rat aquaporin 1, anti-rat aquaporin 2, anti-rat aquaporin 3, and anti-rat aquaporin 4 antibodies were purchased from Alomone Labs, Ltd. (Jerusalem, ...

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Section: Discussionmentioning

confidence: 99%

Increases in the Expression Levels of Aquaporin-2 and Aquaporin-3 in the Renal Collecting Tubules Alleviate Dehydration Associated with Polyuria in Diabetes Mellitus

Satake

Ikarashi

Kagami

et al. 2010

Biological & Pharmaceutical Bulletin

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“…Modulators of AQP1 have been slow to emerge. Antagonists of AQP1 and AQP4 have been described, with a focus on arylsulfonamide compounds including the carbonic anhydrase inhibitor acetazolamide (43) and derivatives of the loop diuretic bumetanide (44). Of particular interest, a 4-aminopyridine carboxamide derivative of the loop diuretic bumetanide (AqB013) was shown to inhibit AQP1 in vitro by acting at an intracellular side that occludes the water pore (44).…”

Section: Pharmacological Agonists Of the Aquaporinsmentioning

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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“…The rationale for their investigation of arylsulfonamides, such as acetazolamide, was reports suggesting acetazolamide inhibition of a different water channel, AQP1 [11][12][13] . However, subsequent measurements in multiple systems in our laboratory 14 and others 15 showed that arylsulfonamides do not inhibit AQP1 water transport.…”

Section: Introductionmentioning

confidence: 99%

Lack of aquaporin-4 water transport inhibition by antiepileptics and arylsulfonamides

Yang

Zhang

Verkman

2008

Bioorganic & Medicinal Chemistry

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Inhibitors of brain glial water channel aquaporin-4 (AQP4) are of potential clinical utility, as they are predicted to modulate brain edema, neuroexcitation and glial scarring. Recently, Huber et al. (Bioorgan. Med. Chem. 2007, 17:1270 2008, in press) reported that a series of arylsulfomamides, antiepileptics, and related small molecules strongly inhibited AQP4 water transport with IC50s down to 1 μM. We retested the compounds with greatest reported potencies, including acetylsulfanilamide, acetazolamide, 6-ethoxy-benzothiazole-2-sulfonamide, topiramate, zonisamide, phenytoin, lamotrigine and sumatriptan, in AQP4-transfected mammalian cells and primary cultures of brain glial cells, using several sensitive assays of osmotic water permeability. Contrary to the findings of Huber et al., in our studies we found no significant inhibition of AQP4 water permeability by any of the compounds at concentrations up to 100 μM.

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Acetazolamide inhibits osmotic water permeability by interaction with aquaporin-1

Cited by 88 publications

References 30 publications

Increases in the Expression Levels of Aquaporin-2 and Aquaporin-3 in the Renal Collecting Tubules Alleviate Dehydration Associated with Polyuria in Diabetes Mellitus

Increases in the Expression Levels of Aquaporin-2 and Aquaporin-3 in the Renal Collecting Tubules Alleviate Dehydration Associated with Polyuria in Diabetes Mellitus

Water transport across the peritoneal membrane

Lack of aquaporin-4 water transport inhibition by antiepileptics and arylsulfonamides

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