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https://www.readbyqxmd.com/read/28614115/trafficking-and-regulation-of-the-nkcc2-cotransporter-in-the-thick-ascending-limb
#1
Kerim Mutig
PURPOSE OF REVIEW: The kidney Na-K-2Cl cotransporter (NKCC2) is essential for urinary concentration and renal electrolyte handling. Loss of function mutations in the NKCC2 gene cause urinary salt and potassium wasting, whereas excessive NKCC2 function has been linked to high blood pressure. Loop diuretics, targeting the transporter, are instrumental for relieving edema or hypertension. This review focuses on intrinsic mechanisms regulating NKCC2 activity at the posttranslational level, namely its trafficking and phosphorylation...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28607127/role-of-the-primary-cilia-on-the-macula-densa-and-thick-ascending-limbs-in-regulation-of-sodium-excretion-and-hemodynamics
#2
Jiangping Song, Lei Wang, Fan Fan, Jin Wei, Jie Zhang, Yan Lu, Yiling Fu, Shaohui Wang, Luis A Juncos, Ruisheng Liu
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2(CRE); IFT88Δ(/flox)), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#3
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
June 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28515172/cross-sex-transplantation-alters-gene-expression-and-enhances-inflammatory-response-in-the-transplanted-kidneys
#4
Lei Wang, Jiangping Song, Shaohui Wang, Jacentha Buggs, Rongjun Chen, Jie Zhang, Liqing Wang, Song Rong, Wenbin Li, Jin Wei, Ruisheng Liu
Kidney transplantation (KTX) is a life-saving procedure for patients with end-stage renal disease. Expression levels of many genes in kidney vary between males and females which may play an essential role in the sex differences in graft function. However, whether these differences are affected after cross-sex-KTX is unknown. In the present study, we assessed post-operative changes in genotype, function and inflammatory responses of the grafts in same-sex and cross-sex-KTX. Single kidney transplants were performed between same and different sex C57BL/6 mice paired into 4 combination groups: female donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male recipient (F/M); and male donor/female recipient (M/F)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#5
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#6
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28274925/salt-supplementation-ameliorates-developmental-kidney-defects-in-cox-2-mice
#7
Patrick Slattery, Stefanie Frölich, Itamar Goren, Rolf Michael Nüsing
Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal time course causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2-/- mice and that salt supplementation corrects these defects. Daily injections of 0.8 mg/g/d NaCl for the first 10 days after birth ameliorated impaired kidney development in COX-2-/- pups resulting in an increase in glomerular size and reduction of immature superficial glomeruli...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28253301/targeting-gene-expression-to-specific-cells-of-kidney-tubules-in-vivo-using-adenoviral-promoter-fragments
#8
Sumiyo Watanabe, Toru Ogasawara, Yoshifuru Tamura, Taku Saito, Toshiyuki Ikeda, Nobuchika Suzuki, Tatsuo Shimosawa, Shigeru Shibata, Ung-Il Chung, Masaomi Nangaku, Shunya Uchida
Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct...
2017: PloS One
https://www.readbyqxmd.com/read/28237360/involvement-of-wnk1-mediated-potassium-channels-in-the-sexual-dimorphism-of-blood-pressure
#9
Guofeng Yu, Mengting Cheng, Wei Wang, Rong Zhao, Zhen Liu
Potassium homeostasis plays an essential role in the control of blood pressure. It is unknown, however, whether potassium balance is involved in the gender-associated blood pressure differences. We therefore investigated the possible mechanism of sexual dimorphism in blood pressure regulation by measuring the blood pressure, plasma potassium, renal actions of potassium channels and upstream regulator in male and female mice. Here we found that female mice exhibited lower blood pressure and higher plasma K(+) level as compared to male littermates...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28228405/inhibition-of-romk-blocks-macula-densa-tubuloglomerular-feedback-yet-causes-renal-vasoconstriction-in-anesthetized-rats
#10
Magali Araujo, William J Welch, Xiaoyan Zhou, Kathleen Sullivan, Shawn Walsh, Alexander Pasternak, Christopher S Wilcox
The Na+/K+/2Cl- cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide. Since outer medullary potassium channel (ROMK) inhibitors prevent reabsorption by NKCC2, we tested the hypothesis that ROMK inhibition with a novel, selective ROMK inhibitor (Compound C) blocks tubuloglomerular feedback (TGF) and reduces vascular resistance. Loop perfusion of either ROMK inhibitor or furosemide caused dose-dependent blunting of TGF, but the response to furosemide was 10-fold more sensitive (IC50= 10-6M for furosemide and IC50=10-5M for Compound C)...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28164127/renal-expression-and-urinary-excretion-of-na-k-2cl-cotransporter-in-obstructive-nephropathy
#11
Anabel Brandoni, Adriana M Torres
Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO) is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2) after 1 (BUO-1), 2 (BUO-2), and 7 (BUO-7) days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28095294/a-novel-slc12a1-gene-mutation-associated-with-hyperparathyroidism-hypercalcemia-nephrogenic-diabetes-insipidus-and-nephrocalcinosis-in-four-patients
#12
Sariya Wongsaengsak, Alaina P Vidmar, Ananta Addala, Elaine S Kamil, Paola Sequeira, Benjamin Fass, Pisit Pitukcheewanont
Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities...
April 2017: Bone
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#13
K I Blankenstein, A Borschewski, R Labes, A Paliege, C Boldt, J A McCormick, D H Ellison, M Bader, S Bachmann, K Mutig
Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
March 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27881573/intestinal-na-k-2cl-cotransporter-2-plays-a-crucial-role-in-hyperosmotic-transitions-of-a-euryhaline-teleost
#14
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
#15
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
#16
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
#17
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...
April 2017: 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
#18
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
#19
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
#20
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
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