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https://www.readbyqxmd.com/read/27881573/intestinal-na-k-2cl-cotransporter-2-plays-a-crucial-role-in-hyperosmotic-transitions-of-a-euryhaline-teleost
#1
Andrew J Esbaugh, Brett Cutler
Euryhaline fishes, such as the red drum (Sciaenops ocellatus), must quickly transition between hyperosmotic and hypoosmotic physiological strategies. When freshwater individuals transition to seawater they are exposed to increased diffusive water loss and ion gain. To maintain osmoregulatory balance these animals must drink and absorb seawater through the intestine, followed by ion excretion at the gills. The ability of fishes to transition between strategies can limit the magnitude of osmotic shock that can be tolerated...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27865300/effect-of-dapagliflozin-treatment-on-fluid-and-electrolyte-balance-in-diabetic-rats
#2
Ling Chen, Lauren M LaRocque, Orhan Efe, Juan Wang, Jeff M Sands, Janet D Klein
AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na(+), K(+), Cl(-) concentration, urine Na(+), K(+), Cl(-) excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin...
November 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27811182/leveraging-unique-structural-characteristics-of-wnk-kinases-to-achieve-therapeutic-inhibition
#3
REVIEW
Jinwei Zhang, Xianming Deng, Kristopher T Kahle
The with-no-lysine (K) WNK kinases are master regulators of the Na(+)-(K(+))-Cl(-) cotransporters, including the renal-specific NCC and NKCC2 cotransporters. The discovery of WNK463, an orally bioavailable pan-WNK kinase inhibitor that exploits unique structural properties of the WNK catalytic domain to achieve high affinity and kinase selectivity, illustrates a strategy of leveraging distinct kinase features to develop specific inhibitors and validates the genetic predictions of the in vivo pharmacology of WNK inhibition...
October 18, 2016: Science Signaling
https://www.readbyqxmd.com/read/27804084/ion-transport-its-regulation-in-the-endolymphatic-sac-suggestions-for-clinical-aspects-of-meniere-s-disease
#4
REVIEW
Nozomu Mori, Takenori Miyashita, Ryuhei Inamoto, Ai Matsubara, Terushige Mori, Kosuke Akiyama, Hiroshi Hoshikawa
Ion transport and its regulation in the endolymphatic sac (ES) are reviewed on the basis of recent lines of evidence. The morphological and physiological findings demonstrate that epithelial cells in the intermediate portion of the ES are more functional in ion transport than those in the other portions. Several ion channels, ion transporters, ion exchangers, and so on have been reported to be present in epithelial cells of ES intermediate portion. An imaging study has shown that mitochondria-rich cells in the ES intermediate portion have a higher activity of Na(+), K(+)-ATPase and a higher Na(+) permeability than other type of cells, implying that molecules related to Na(+) transport, such as epithelial sodium channel (ENaC), Na(+)-K(+)-2Cl(-) cotransporter 2 (NKCC2) and thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), may be present in mitochondria-rich cells...
November 1, 2016: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/27707706/solute-transport-and-oxygen-consumption-along-the-nephrons-effects-of-na-transport-inhibitors
#5
Anita T Layton, Kamel Laghmani, Volker Vallon, Aurélie Edwards
Sodium and its associated anions are the major determinant of extracellular fluid volume, and the reabsorption of Na(+) by the kidney plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na(+) transport (TNa) along the nephron alter urinary solute excretion and TNa efficiency and how those effects may vary along different nephron segments. To accomplish that goal, we used the multinephron model developed in the companion study (28)...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27706697/effect-of-polychlorinated-biphenyls-on-osmoregulatory-response-and-apoptosis-in-gift-tilapia-oreochromis-niloticus
#6
Y Zheng, L Qiu, L Fan, C Song, S Meng, J Chen
In the present study, GIFT tilapia Oreochromis niloticus were exposed to polychlorinated biphenyls (PCBs) for 7, 14, and 21 days. Over the duration of the exposure, genotoxicity and the activity of Na(+)/K(+)-ATPase (NKA) and Ca(+)/Mg(+)-ATPase (CMA) were measured in the gill, kidney, and intestine, to evaluate changes in osmoregulatory response in O. niloticus. Our results showed significant decreases in organic NKA (except in gill tissues after 0.5 mg/L PCB-exposure) and CMA activity. The results of the genotoxicity assay showed significant increases in atp1a1a, nkcc2 (only in gill tissue), and fxyd7 (except after 21 days of 5 mg/L PCB exposure)...
September 2, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27681558/vasopressin-lowers-renal-epoxyeicosatrienoic-acid-levels-by-activating-soluble-epoxide-hydrolase
#7
Christin Boldt, Tom Röschel, Nina Himmerkus, Allein Plain, Markus Bleich, Robert Labes, Maximilian Blum, Hans Krause, Ahmed Magheli, Torsten Giesecke, Kerim Mutig, Michael Rothe, Steven M Weldon, Duska Dragun, Wolf-Hagen Schunck, Sebastian Bachmann, Alexander Paliege
Activation of the thick ascending limb (TAL) Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27551042/vesicle-associated-membrane-protein-3-vamp3-mediates-constitutive-trafficking-of-the-renal-co-transporter-nkcc2-in-thick-ascending-limbs-role-in-renal-function-and-blood-pressure
#8
Paulo S Caceres, Mariela Mendez, Mohammed Z Haque, Pablo A Ortiz
Renal cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na(+)/K(+)/2Cl(-) co-transporter NKCC2. Trafficking of NKCC2 to the apical surface regulates NKCC2-mediated NaCl absorption and blood pressure. The molecular mechanisms by which NKCC2 reaches the apical surface and their role in renal function and maintenance of blood pressure are poorly characterized. Here we report that NKCC2 interacts with the vesicle fusion protein VAMP3, and they co-localize at the TAL apical surface. We observed that silencing VAMP3 in vivo blocks constitutive NKCC2 exocytic delivery, decreasing the amount of NKCC2 at the TAL apical surface...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27517916/serum-and-glucocorticoid-regulated-kinase-1-in-sodium-homeostasis
#9
REVIEW
Yiyun Lou, Fan Zhang, Yuqin Luo, Liya Wang, Shisi Huang, Fan Jin
The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and type A natriuretic peptide receptor (NPR-A)...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27508833/-op-7c-01-uromodulin-nacl-interaction-on-mrna-expression-of-ion-transporters-in-isolated-tubules-of-umod-and-umod-mice
#10
L Graham, D Graham, M W McBride, A F Dominiczak, S Padmanabhan
OBJECTIVE: UMOD-/- mice have low blood pressure and decreased salt-sensitivity indicating interactions between UMOD and sodium transport in the TAL. However, it's unclear whether the effect of UMOD is solely through interaction with cognate molecules in the TAL or whether the perturbations in physiology are more complex with involvement of both TAL and other parts of the nephron. We propose to answer this by profiling mRNA expression levels of the main ion transporters and signalling molecules in tubules from UMOD+/+ and UMOD-/- mice...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27508610/-op-2a-02-uromodulin-modulates-the-effect-of-salt-on-blood-pressure-in-the-general-population
#11
B Ponte, M Pruijm, I Guessous, D Ackermann, G Ehret, M Mohaupt, F Paccaud, B Vogt, P Y Martin, A Pechere-Berstschi, M Burnier, O Devuyst, M Bochud
OBJECTIVE: Genome wide association studies have shown that the gene encoding for uromodulin (UMOD) is associated with hypertension. Recently, animal studies have demonstrated that UMOD modulates NaCl reabsorption driven by NKCC2. We hypothesised that the NaCl effect on blood pressure may be modulated by UMOD levels in the general population. DESIGN AND METHOD: Urinary UMOD levels were measured in 994 participants of the SKIPOGH population-based study who completed 24 h blood pressure monitoring and 24 h urinary collection...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27478876/metformin-improves-urine-concentration-in-rodents-with-nephrogenic-diabetes-insipidus
#12
Orhan Efe, Janet D Klein, Lauren M LaRocque, Huiwen Ren, Jeff M Sands
Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/ kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily...
July 21, 2016: JCI Insight
https://www.readbyqxmd.com/read/27465993/the-ep3-receptor-regulates-water-excretion-in-response-to-high-salt-intake
#13
Shoujin Hao, AnnMarie DelliPizzi, Mariana Quiroz-Munoz, Houli Jiang, Nicholas R Ferreri
The mechanisms by which prostanoids contribute to the maintenance of whole body water homeostasis are complex and not fully understood. The present study demonstrates that an EP3-dependent feedback mechanism contributes to the regulation of water homeostasis under high-salt conditions. Rats on a normal diet and tap water were placed in metabolic cages and given either sulprostone (20 μg·kg(-1)·day(-1)) or vehicle for 3 days to activate EP3 receptors in the thick ascending limb (TAL). Treatment was continued for another 3 days in rats given either 1% NaCl in the drinking water or tap water...
October 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27443990/renal-sodium-transport-in-renin-deficient-dahl-salt-sensitive-rats
#14
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Carol Moreno, Alexander Staruschenko
OBJECTIVE: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat. METHODS: Renin knockout (Ren(-/-)) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na(+) transporters...
July 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27442254/prostaglandin-e2-mediated-increase-in-calcium-and-phosphate-excretion-in-a-mouse-model-of-distal-nephron-salt-wasting
#15
Manoocher Soleimani, Sharon Barone, Jie Xu, Saeed Alshahrani, Marybeth Brooks, Francis X McCormack, Roger D Smith, Kamyar Zahedi
Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion...
2016: PloS One
https://www.readbyqxmd.com/read/27413200/sgk1-dependent-enac-processing-and-trafficking-in-mice-with-high-dietary-k-intake-and-elevated-aldosterone
#16
Lei Yang, Gustavo Frindt, Florian Lang, Dietmar Kuhl, Volker Vallon, Lawrence G Palmer
We examined renal Na and K transporters in mice with deletions in the gene encoding the aldosterone-induced protein SGK1. The knockout mice were hyperkalemic, and had altered expression of the subunits of the epithelial Na channel (ENaC). The kidneys showed decreased expression of the cleaved forms of the γENaC subunit, and the fully glycosylated form of the βENaC subunits when animals were fed a high-K diet. Knockout animals treated with exogenous aldosterone also had reduced subunit processing and diminished surface expression of βENaC and γENaC...
July 13, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27363030/albuminuria-confers-renal-resistance-to-loop-diuretics-via-the-stimulation-of-nlrp3-inflammasome-prostaglandin-signaling-in-thick-ascending-limb
#17
Yibo Zhuang, Zhanjun Jia, Caiyu Hu, Guixia Ding, Xintong Zhang, Yue Zhang, Guangrui Yang, Rajeev Rohatgi, Songming Huang, John Ci-Jiang He, Aihua Zhang
Renal resistance to loop diuretics is a frequent complication in a number of kidney disease patients with elusive mechanism. Employing human renal biopsy specimens, albumin overload mouse model, and primary cultures of mouse renal tubular cells, albuminuria effect on NKCC2 expression and function and the underlying mechanisms were investigated. In the renal biopsy specimens of albuminuric patients, we found that NKCC2 was significantly downregulated with a negative correlation with albuminuria severity as examined by immunohistochemistry...
June 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27306979/demonstration-of-the-functional-impact-of-vasopressin-signaling-in-the-thick-ascending-limb-by-a-targeted-transgenic-rat-approach
#18
Kerim Mutig, Tordis Borowski, Christin Boldt, Aljona Borschewski, Alexander Paliege, Elena Popova, Michael Bader, Sebastian Bachmann
The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear...
August 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27213818/spilanthol-from-acmella-oleracea-lowers-the-intracellular-levels-of-camp-impairing-nkcc2-phosphorylation-and-water-channel-aqp2-membrane-expression-in-mouse-kidney
#19
Andrea Gerbino, Giorgia Schena, Serena Milano, Luigi Milella, Alan Franco Barbosa, Francesca Armentano, Giuseppe Procino, Maria Svelto, Monica Carmosino
Acmella oleracea is well recognized in Brazilian traditional medicine as diuretic, although few scientific data have been published to support this effect. Aim of this study was to determine the molecular effect of Acmella oleracea extract and its main alkylamide spilanthol on two major processes involved in the urine concentrating mechanism: Na-K-2Cl symporter (NKCC2) activity in the thick ascending limb and water channel aquaporin 2 accumulation at the apical plasma membrane of collecting duct cells. Phosphorylation of NKCC2 was evaluated as index of its activation by Western blotting...
2016: PloS One
https://www.readbyqxmd.com/read/27168439/mage-d2-and-the-regulation-of-renal-salt-transporters
#20
EDITORIAL
Nine V A M Knoers, René J Bindels
No abstract text is available yet for this article.
May 12, 2016: New England Journal of Medicine
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