Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

Sasaki, Sei; Fushimi, Kiyohide; Saito, Hideki; Saito, Fumiko; Uchida, Shinichi; Ishibashi, Keiichiro; Kuwahara, Michio; Ikeuchi, Tatsuro; Inui, Kentaro; Nakajima, Kensuke

doi:10.1172/jci117079

Cited by 206 publications

(99 citation statements)

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“…5,6) Secreted AVP from the pituitary gland binds to V 2 receptors located in the basolateral membrane of principal cells in the collecting ducts, and then the activated V 2 receptors trigger the transport of AQP2 from intracellular storage vesicles into the apical membrane. The amount of AQP2 activated determines the water permeability in the apical membrane and then dominates urinary concentrating ability.…”

Section: Article P533mentioning

confidence: 99%

Aquaporin-2-Guided Tolvaptan Therapy in Patients With Congestive Heart Failure Accompanied by Chronic Kidney Disease

Imamura

2014

Int. Heart J.

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R ecently, there has been increasing evidence supporting the efficacy and safety of the arginine vasopressin (AVP) type 2 (V 2 ) antagonist tolvaptan (TLV) in the improvement of hyponatremia or amelioration of congestion sparing renal function in acute/chronic heart failure (HF) patients refractory to considerable amounts of loop diuretics. 1)However, such a clinical benefit of TLV-incorporated diuretic therapy is not necessarily observed in all HF patients. In other words, we sometimes experience non-responders to TLV, whose clinical course worsens regardless of the initiation of TLV. 2)Although the precise mechanism of resistance to TLV is unknown, we previously speculated that aging and chronic kidney disease (CKD) were major risk factors of non-responders.3) In fact, concentrating and diluting ability in the collecting ducts is essential for the efficacy of TLV, but is often impaired in elderly or those with advanced CKD. However, according to our clinical experience, there were several responders to TLV even though they were complicated with stage G4 CKD. Article p.533The efficacy of TLV treatment in patients with CKD is controversial. Sato, et al demonstrated in a recent study that some responders with diabetes mellitus nephropathy received a clinical benefit from TLV treatment even though their renal dysfunction was approximately equivalent to stage G4 CKD (22.1 ± 18.1 mL/minute/1.73m 2 of estimated glomerular filtration ratio). 4) Among the 8 patients from whom renal specimens were obtained, 7 were responders and simultaneously had explicit expression of aquaporin-2 (AQP2) in the collecting ducts. The remaining patient was a non-responder showing no expression of AQP2 with histological evidence of tubulointerstitial damage. Although the sample number was very small, they speculated that some, albeit not all, patients with advanced CKD did respond to TLV, and that the responses to TLV might be dependent on residual expression of AQP2 in the collecting ducts.AQP2 is the recently characterized AVP-regulated water channel expressed in the collecting ducts in the kidney.5,6) Secreted AVP from the pituitary gland binds to V 2 receptors located in the basolateral membrane of principal cells in the collecting ducts, and then the activated V 2 receptors trigger the transport of AQP2 from intracellular storage vesicles into the apical membrane. The amount of AQP2 activated determines the water permeability in the apical membrane and then dominates urinary concentrating ability. 7) Expression of AQP2 in the apical membrane is considered as an index of the V2-receptor dependent activity of the collecting ducts, which may be essential for the response to TLV because TLV cannot block water-reabsorption there without baseline expression or activation of AQP2 protein.Considering the above mechanism, AQP2 can be a good marker for predicting responses to TLV especially in patients with CKD. However, how can we measure the expression of AQP2 in the human kidney? Sato, et al obtained renal biopsy specimens and demonstrated ...

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Section: Article P533mentioning

confidence: 99%

Aquaporin-2-Guided Tolvaptan Therapy in Patients With Congestive Heart Failure Accompanied by Chronic Kidney Disease

Imamura

2014

Int. Heart J.

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“…The mechanism for the appearance of NDI symptoms in female carriers is explained by an extremely skewed inactivation of the normal allele of the X chromosome [24]; the frequency of this event was estimated to be very rare [9]. However, a recent study by Sato et al [25] showed that a moderately skewed inactivation of the normal allele is enough to cause NDI symptoms.…”

Section: Frequency Of Symptomatic Carriers Of Avpr2 Mutationsmentioning

confidence: 99%

“…After the cloning of human AQP2 [9] and the first report of an NDI patient with mutated AQP2 [10], we have performed gene mutation analyses of Japanese NDI patients. At the end of July 2012, the total number of analyzed NDI families was 78, a significant number which may provide some insights into the genetic causes of hereditary NDI.…”

Section: Introductionmentioning

confidence: 99%

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

et al. 2012

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Background Familial form of nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90 % of NDI families carry disease-causing mutations in AVPR2 and 10 % carry the mutations in AQP2; however, these percentages have not been supported by actual data. It is also unknown whether these percentages vary in different ethnic groups. Methods Gene mutation analyses were performed for 78 Japanese NDI families. All exons and intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced. Results A total of 62 families (79 %) carried diseasecausing mutations in AVPR2, while nine families (12 %) carried mutations in AQP2. We identified 22 novel putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding AVPR2, 52 disease-causing mutations were identified. Among them, missense mutations were most common (54 %), followed by deletion mutations. In the 64 women who had monoallelic disease-causing AVPR2 mutations, 16 (25 %) had NDI symptoms, including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations were identified in nine families. Two missense mutations and one deletion mutation showed a recessive inheritance, while one missense mutation and five small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance.Conclusions Most Japanese NDI families carry diseasecausing mutations in AVPR2 and 12 % carry mutations in AQP2. A total of 22 novel putatively disease-causing mutations were identified. The relatively high occurrence of symptomatic carriers of AVPR2 mutations needs attention.

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“…Shortly after, the AQP2 gene encoding the vasopressin-regulated water channel aquaporin-2 (AQP2) was cloned [8,9] and in 1994 mutations in AQP2 were found to underlie the rare autosomal forms of DI [10]. The discovery of these key molecules allowed the development of targeted drugs.…”

Section: Introductionmentioning

confidence: 99%

Urinary concentration: different ways to open and close the tap

Böckenhauer

Bichet

2013

Pediatr Nephrol

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Nephrogenic diabetes insipidus (NDI) provides an excellent model for the benefits and insights that can be gained from studying rare diseases. The discovery of underlying genes identified key molecules involved in urinary concentration, including the type 2 vasopressin receptor AVPR2 and the water channel AQP2, which constitute obvious pharmacologic targets. Subsequently developed drugs targeting AVPR2 not only provide potential benefit to some patients with NDI, but are now used for much more common clinical applications as diverse as nocturnal enuresis and heart failure. Yet, the story is still evolving:clinical observations and animal experiments continue to discover new ways to affect urinary concentration. These novel pathways can potentially be exploited for therapeutic gain. Here we review the (patho)physiology of water homoeostasis, the current status of clinical management and potential new treatments.3

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Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

Abstract: We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for

Cited by 206 publications

References 36 publications

Aquaporin-2-Guided Tolvaptan Therapy in Patients With Congestive Heart Failure Accompanied by Chronic Kidney Disease

Aquaporin-2-Guided Tolvaptan Therapy in Patients With Congestive Heart Failure Accompanied by Chronic Kidney Disease

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

Urinary concentration: different ways to open and close the tap

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