The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells—a Potential Target for Pharmacological Intervention in Cardiovascular Diseases

Vukićević, Tanja; Schulz, Maike Svenja; Faust, Dörte; Klussmann, Enno

doi:10.3389/fphar.2016.00023

Cited by 49 publications

(52 citation statements)

References 403 publications

(286 reference statements)

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“…The clinical relevance of our findings is demonstrated by the fact that while in patients suffering from CDI the administration of dDAVP is the treatment of choice, it may be beneficial to administer as a supplementary therapy agents that are known to correct the AQP2 apical translocation defect such as statins or the JAK-2 and EFGR inhibitor AG-490 which both have been shown to be effective in Brattleboro rats. 35 This may indeed be an effective treatment strategy taking into account our findings that treatment of with dDAVP leads to increased AQP3 gene expression as well as protein levels in the plasma membrane of principal cells. So an approach that improves AQP2 and AQP3 turnover in the plasma membrane as suggested above, could prove beneficial to the clinical setting with respect to DI patients.…”

Section: Omcd Principal Cells Of Avp-deficient Brattleboro and Water-mentioning

confidence: 93%

Brattleboro rats have impaired apical membrane water permeability regulation in the outer medullary collecting duct principal cells

Baturina

Katkova

Zarogiannis

et al. 2016

Clin Exp Pharma Physio

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Vasopressin (AVP) regulates the body salt-water balance. Brattleboro rats carry an AVP gene mutation resulting in a recessive form of central diabetes insipidus, being ideal for AVP deficiency studies. Herein, we studied the water permeability of the apical and basolateral sides of outer medullary collecting duct (OMCD) principal cells in response to dDAVP (a V2 receptor agonist) administration in Wistar and Brattleboro rats. Biophysical measurements of the water permeability (P ) of isolated OMCD principal cells were performed with the calcein quenching method with/without dDAVP (10 mol/L). mRNA transcripts and protein levels of AQP2, AQP3 and AQP4 were assessed by RT-PCR and western blot respectively. dDAVP increased the apical and basolateral P of OMCD principal cells in Wistar rats, while in Brattleboro rats this effect was present basolaterally. Long-term dDAVP administration in both strains resulted in a significant increase in mRNA expression of all assessed AQP's while only the protein levels of AQP2 and AQP3 were significantly increased. Short-term (20 minutes) dDAVP treatment of isolated OMCD fragments resulted in significantly increased plasma membrane expression of AQP2 in Wistar rats and of AQP2 and AQP3 in Brattleboro rats. In summary, dDAVP induces different expression of AQP2, AQP3 and AQP4 in Wistar and Brattleboro rats during short- and long-term treatment. In Wistar rats dDAVP mainly increased AQP2 expression while in Brattleboro rats it increased functional water permeability mainly by AQP3 expression.

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Section: Omcd Principal Cells Of Avp-deficient Brattleboro and Water-mentioning

confidence: 93%

Brattleboro rats have impaired apical membrane water permeability regulation in the outer medullary collecting duct principal cells

Baturina

Katkova

Zarogiannis

et al. 2016

Clin Exp Pharma Physio

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“…One of the main causes is long-term lithium treatment of bipolar disorders. This causes acquired NDI in up to 40% of the patients [18] .…”

Section: -Biologicals For Aquaporin Detection and Regulationmentioning

confidence: 99%

“…Several AQPs are implicated in other forms of edema (ocular edema, pulmonary edema, peripheral edema and systemic edema), and thus modulating aquaporin channel expression in mammals has been proposed to revert fluid accumulation associated with edema [65] . disorders that are not encompassed by the herein patent review can be found in [18] . blindness.…”

Section: -Biologicals For Aquaporin Detection and Regulationmentioning

confidence: 99%

“…The disease can be acquired or inherited, and is characterized by polyuria and polydipsia. Inversely, up-regulation of the system causing a predominant localization of AQP2 in the plasma membrane leads to excessive water retention and hyponatremia as in the syndrome of inappropriate antidiuretic hormone secretion (SIADH), late stage heart failure or liver cirrhosis [18] .…”

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confidence: 99%

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Aquaporin modulators: a patent review (2010–2015)

Soveral

Casini

2016

Expert Opinion on Therapeutic Patents

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Since the discovery of aquaporin-1 (AQP1) as a water channel, more than 2,000 articles, reviews and chapters have been published. The wide tissue expression, functional and biological roles have documented the major and essential physiological importance of these channels both in health and disease. Thus, over the years, studies have revealed essential importance of aquaporins in mammalian pathophysiology revealing aquaporins as potential drug targets. Areas covered: Starting from a brief description of the main structural and functional features of aquaporins, their roles in physiology and pathophysiology of different human diseases, this review describes the main classes of small molecules and biologicals patented, published from 2010 to 2015, able to regulate AQPs for diagnostic and therapeutic applications. Expert opinion: Several patents report on AQP modulators, mostly inhibitors, and related pharmaceutical formulations, to be used for treatments of water imbalance disorders, such as edema. Noteworthy, a unique class of gold-based compounds as selective inhibitors of aquaglyceroporin isoforms may provide new chemical tools for therapeutic applications, especially in cancer. AQP4-targeted therapies for neuromyelitis optica, enhancement of AQP2 function for nephrogenic diabetes insipidus and AQP1-5 gene transfer for the Sjogren's syndrome represent promising therapies that deserve further investigation by clinical trials.

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“…Vasopressin (VP)-mediated apical accumulation of aquaporin 2 (AQP2) is crucial for water reabsorption and urine concentration in the kidney collecting duct [1][2][3][4]. To initiate this process, VP induces changes in the phosphorylation state of AQP2 at several serine residues [5,6].…”

Section: Introductionmentioning

confidence: 99%

Chlorpromazine Induces Basolateral Aquaporin-2 Accumulation via F-Actin Depolymerization and Blockade of Endocytosis in Renal Epithelial Cells

Bouley

Yui

Terlouw

et al. 2020

Cells

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We previously showed that in polarized Madin-Darby canine kidney (MDCK) cells, aquaporin-2 (AQP2) is continuously targeted to the basolateral plasma membrane from which it is rapidly retrieved by clathrin-mediated endocytosis. It then undertakes microtubule-dependent transcytosis toward the apical plasma membrane. In this study, we found that treatment with chlorpromazine (CPZ, an inhibitor of clathrin-mediated endocytosis) results in AQP2 accumulation in the basolateral, but not the apical plasma membrane of epithelial cells. In MDCK cells, both AQP2 and clathrin were concentrated in the basolateral plasma membrane after CPZ treatment (100 µM for 15 min), and endocytosis was reduced. Then, using rhodamine phalloidin staining, we found that basolateral, but not apical, F-actin was selectively reduced by CPZ treatment. After incubation of rat kidney slices in situ with CPZ (200 µM for 15 min), basolateral AQP2 and clathrin were increased in principal cells, which simultaneously showed a significant decrease of basolateral compared to apical F-actin staining. These results indicate that clathrin-dependent transcytosis of AQP2 is an essential part of its trafficking pathway in renal epithelial cells and that this process can be inhibited by selectively depolymerizing the basolateral actin pool using CPZ.Cells 2020, 9, 1057 2 of 18 mechanisms of water channel accumulation in the apical plasma membrane of collecting duct cells have been of particular interest, the regulation of basolateral AQP2 has also been investigated in several studies [22][23][24][25][26]. In the cortical connecting segment, basolateral AQP2 is usually readily detectable [23], and AQP2 has varying levels of basolateral expression in collecting duct principal cells from kidney cortex to medulla, with the most obvious basolateral expression in the inner medulla. In MDCK cells, derived from canine kidney, transfected AQP2 usually accumulates in the apical membrane upon intracellular cAMP elevation. However, AQP2 instead concentrates on the basolateral membrane after forskolin (FK) treatment under hypertonic conditions [26]. Importantly, Sec6, Sec8, and RalA, all components of the exocyst, which targets proteins to the basolateral plasma membrane [27], were associated with AQP2-containing vesicles upon mass spectrometry analysis [28]. Furthermore, we showed that AQP2 is necessary for cell migration and tubule morphogenesis through its RGD-regulated interaction with basolateral integrin-β1 [29]. These previous findings all pointed to the existence of an AQP2 basolateral targeting pathway, and indeed we demonstrated the existence of a transcytotic pathway for AQP2 in MDCK cells by blocking basolateral AQP2 during its transit through this membrane domain using low temperature [30]. After initial basolateral targeting, AQP2 is retrieved into Rab5-positive vesicles, then undertakes microtubule-dependent transcytosis to apical recycling vesicles [30]. This novel trafficking concept is supported by an apical plasma membrane proteomics study using mpkCCD cel...

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The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells—a Potential Target for Pharmacological Intervention in Cardiovascular Diseases

Cited by 49 publications

References 403 publications

Brattleboro rats have impaired apical membrane water permeability regulation in the outer medullary collecting duct principal cells

Brattleboro rats have impaired apical membrane water permeability regulation in the outer medullary collecting duct principal cells

Aquaporin modulators: a patent review (2010–2015)

Chlorpromazine Induces Basolateral Aquaporin-2 Accumulation via F-Actin Depolymerization and Blockade of Endocytosis in Renal Epithelial Cells

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