Na K 2Cl cotransporter

Summary

Gene Symbol: Na K 2Cl cotransporter
Description: solute carrier family 12 member 1
Alias: BSC1, NKCC2, solute carrier family 12 member 1, NKCC2A variant A, Na-K-2Cl cotransporter, bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2, kidney-specific Na-K-Cl symporter, solute carrier family 12 (sodium/potassium/chloride transporter), member 1, solute carrier family 12 (sodium/potassium/chloride transporters), member 1
Species: human
Products:     Na K 2Cl cotransporter

Top Publications

  1. Simon D, Karet F, Hamdan J, DiPietro A, Sanjad S, Lifton R. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. 1996;13:183-8 pubmed
    ..We demonstrate linkage of Bartter's syndrome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frameshift or non-conservative missense mutations for this gene that co-segregate with the disease...
  2. Pisitkun T, Shen R, Knepper M. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004;101:13368-73 pubmed
    ..The results indicate that exosome isolation may provide an efficient first step in biomarker discovery in urine. ..
  3. Lou Y, Zhang F, Luo Y, Wang L, Huang S, Jin F. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis. Int J Mol Sci. 2016;17: pubmed publisher
    ..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 ..
  4. Lang F, Vallon V. Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport. Clin Exp Nephrol. 2012;16:73-80 pubmed publisher
    ..Thus, SGK1 has a profound effect on K(+) homeostasis and on a multitude of K(+)-sensitive cellular functions. ..
  5. Zhou X, Zhang Z, Shin M, Horwitz S, Levorse J, Zhu L, et al. Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure. Hypertension. 2013;62:288-94 pubmed publisher
    ..Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation. ..
  6. Hunter R, Moorhouse R, Farrah T, Macintyre I, Asai T, Gallacher P, et al. First-in-Man Demonstration of Direct Endothelin-Mediated Natriuresis and Diuresis. Hypertension. 2017;70:192-200 pubmed publisher
    ..free water clearance and tended to increase the abundance of the sodium-potassium-chloride cotransporter (NKCC2) in urinary extracellular vesicles. Our protocol induced modest increases in circulating and urinary ET-1...
  7. Jaggi A, Kaur A, Bali A, Singh N. Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases. Curr Neuropharmacol. 2015;13:369-88 pubmed
    ..NKCC1 is widely distributed throughout the body, while NKCC2 is exclusively present in kidney...
  8. McCormick J, Yang C, Zhang C, Davidge B, Blankenstein K, Terker A, et al. Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. J Clin Invest. 2014;124:4723-36 pubmed publisher
  9. Kortenoeven M, Pedersen N, Rosenbaek L, Fenton R. Vasopressin regulation of sodium transport in the distal nephron and collecting duct. Am J Physiol Renal Physiol. 2015;309:F280-99 pubmed publisher
    ..transport and summarize the effects of AVP on various molecular targets, including the sodium-potassium-chloride cotransporter NKCC2, the thiazide-sensitive sodium-chloride cotransporter NCC, and the epithelial sodium channel ENaC.

More Information

Publications123 found, 100 shown here

  1. de Bragança A, Moreau R, de Brito T, Shimizu M, Canale D, de Jesus D, et al. Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage. PLoS ONE. 2017;12:e0179199 pubmed publisher
    ..AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs...
  2. Qian M, Han S, Yu Z, Chen X. [Poor weight gain, recurrent metabolic alkalosis and hypokalemia in a neonate]. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19:812-815 pubmed
    ..A definite diagnosis of neonatal Bartter syndrome can be made based on the presence of SLC12A1 gene mutation. ..
  3. Foulke Abel J, In J, Yin J, Zachos N, Kovbasnjuk O, Estes M, et al. Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology. Gastroenterology. 2016;150:638-649.e8 pubmed publisher
    ..The duodenal enteroid model showed that electrogenic Na(+)/HCO3(-) cotransporter 1 might be a target in the intestinal mucosa for treatment of secretory diarrheas. ..
  4. Taguchi K, Hamamoto S, Okada A, Unno R, Kamisawa H, Naiki T, et al. Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers. J Am Soc Nephrol. 2017;28:333-347 pubmed publisher
    ..This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs. ..
  5. Claramunt D, Gil Peña H, Fuente R, Garcia Lopez E, Hernández Frías O, Ordoñez F, et al. Effects of growth hormone treatment on growth plate, bone, and mineral metabolism of young rats with uremia induced by adenine. Pediatr Res. 2017;82:148-154 pubmed publisher
    ..ConclusionGH treatment accelerated longitudinal growth velocity, stimulated the proliferation and enlargement of chondrocytes, and did not modify the elevated serum PTH or FGF23 concentrations or the abnormal bone structure...
  6. Henderson S, Wege S, Qiu J, Blackmore D, Walker A, Tyerman S, et al. Grapevine and Arabidopsis Cation-Chloride Cotransporters Localize to the Golgi and Trans-Golgi Network and Indirectly Influence Long-Distance Ion Transport and Plant Salt Tolerance. Plant Physiol. 2015;169:2215-29 pubmed publisher
    ..Our findings indicate that CCC function is conserved between grapevine and Arabidopsis, but neither protein is likely to directly mediate ion transfer with the xylem or have a direct role in salt tolerance. ..
  7. Lang F, Huang D, Vallon V. SGK, renal function and hypertension. J Nephrol. 2010;23 Suppl 16:S124-9 pubmed
    ..the activity of a variety of ion channels such as ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and ClCKb; carriers such as NHE3, NKCC2, NCC and SGLT1; as well as the Na+/K+-ATPase...
  8. Pavlov T, Levchenko V, Ilatovskaya D, Moreno C, Staruschenko A. Renal sodium transport in renin-deficient Dahl salt-sensitive rats. J Renin Angiotensin Aldosterone Syst. 2016;17: pubmed publisher
    ..involved in Na(+) absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle...
  9. Xu C, Tan S, Zhang J, Seubert C, Gravenstein N, Sumners C, et al. Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists. Psychoneuroendocrinology. 2015;60:173-81 pubmed publisher
    ..Sevoflurane-enhanced neuronal excitation and elevated corticosteroid levels at the time of anesthesia contribute to the mechanisms initiating neonatal sevoflurane-induced long-term endocrine and neurobehavioral abnormalities. ..
  10. Sharma N, Li L, Ecelbarger C. Sex differences in renal and metabolic responses to a high-fructose diet in mice. Am J Physiol Renal Physiol. 2015;308:F400-10 pubmed publisher
    ..These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption. ..
  11. Malaque C, de Bragança A, Sanches T, Volpini R, Shimizu M, Hiyane M, et al. The role of dexamethasone in scorpion venom-induced deregulation of sodium and water transport in rat lungs. Intensive Care Med Exp. 2015;3:28 pubmed publisher
    ..Our results suggest that T. serrulatus venom and dexamethasone both regulate sodium transport in the lung and that T serrulatus venom regulates sodium transport via the TLR4 pathway. ..
  12. Simard J, Kahle K, Gerzanich V. Molecular mechanisms of microvascular failure in central nervous system injury--synergistic roles of NKCC1 and SUR1/TRPM4. J Neurosurg. 2010;113:622-9 pubmed publisher
  13. Wang S, Zhang X, Song C, Xiao T, Zhao M, Zhu G, et al. In vivo effects of bumetanide at brain concentrations incompatible with NKCC1 inhibition on newborn DGC structure and spontaneous EEG seizures following hypoxia-induced neonatal seizures. Neuroscience. 2015;286:203-15 pubmed publisher
    ..These effects of bumetanide may be mediated by the targets outside the BBB-protected central nerve system (CNS) or CNS-located target(s) other than NKCC1. ..
  14. Karim S, Al Maghrabi J, Farsi H, Al Sayyad A, Schulten H, Buhmeida A, et al. Cyclin D1 as a therapeutic target of renal cell carcinoma- a combined transcriptomics, tissue microarray and molecular docking study from the Kingdom of Saudi Arabia. BMC Cancer. 2016;16:741 pubmed
    ..Further in vivo and in vitro molecular studies are needed to investigate the therapeutic target potential of CCND1 for RCC treatment. ..
  15. Montes S, Castro Chávez A, Florian Soto C, Heras Romero Y, Ríos C, Rivera Mancía S. Bumetanide increases manganese accumulation in the brain of rats with liver damage. Eur J Pharmacol. 2016;774:127-34 pubmed publisher
  16. Laghmani K, Beck B, Yang S, Seaayfan E, Wenzel A, Reusch B, et al. Polyhydramnios, Transient Antenatal Bartter's Syndrome, and MAGED2 Mutations. N Engl J Med. 2016;374:1853-63 pubmed publisher
    ..We showed that MAGE-D2 affects the expression and function of the sodium chloride cotransporters NKCC2 and NCC (key components of salt reabsorption in the distal renal tubule), possibly through adenylate cyclase and ..
  17. Cairns S, Borrani F. β-Adrenergic modulation of skeletal muscle contraction: key role of excitation-contraction coupling. J Physiol. 2015;593:4713-27 pubmed publisher
    ..The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans. ..
  18. Kamat N, Thabet S, Xiao L, Saleh M, Kirabo A, Madhur M, et al. Renal transporter activation during angiotensin-II hypertension is blunted in interferon-γ-/- and interleukin-17A-/- mice. Hypertension. 2015;65:569-76 pubmed publisher
  19. Tomas J, Mulet C, Saffarian A, Cavin J, Ducroc R, Regnault B, et al. High-fat diet modifies the PPAR-? pathway leading to disruption of microbial and physiological ecosystem in murine small intestine. Proc Natl Acad Sci U S A. 2016;113:E5934-E5943 pubmed
    ..Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-?-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses. ..
  20. Ma L, Liu Y, Landry N, El Achkar T, Lieske J, Wu X. Point mutation in D8C domain of Tamm-Horsfall protein/uromodulin in transgenic mice causes progressive renal damage and hyperuricemia. PLoS ONE. 2017;12:e0186769 pubmed publisher
    ..apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1...
  21. Theilig F, Wu Q. ANP-induced signaling cascade and its implications in renal pathophysiology. Am J Physiol Renal Physiol. 2015;308:F1047-55 pubmed publisher
    ..Characteristics of ANP resistance and corin deficiency are also encountered in patients with edema-associated diseases, highlighting the importance of ANP signaling in salt-water balance and renal pathophysiology. ..
  22. Zikos A, Seale A, Lerner D, Grau E, Korsmeyer K. Effects of salinity on metabolic rate and branchial expression of genes involved in ion transport and metabolism in Mozambique tilapia (Oreochromis mossambicus). Comp Biochem Physiol A Mol Integr Physiol. 2014;178:121-31 pubmed publisher
    ..These results suggest that the energetic costs of osmoregulation are higher in SW than in FW, which may be related to the salinity-dependent differences in osmoregulatory mechanisms found in the gills of Mozambique tilapia. ..
  23. Kim Y, Kim Y, Kim W, Lee S, Oh S, Han H, et al. Histamine 1 receptor-G??-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock. Mol Brain. 2016;9:49 pubmed publisher
    ..This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system. ..
  24. Davies M, Gleich K, Katerelos M, Lee M, Mount P, Power D. The Thiazide-Sensitive Co-Transporter Promotes the Development of Sodium Retention in Mice with Diet-Induced Obesity. Kidney Blood Press Res. 2015;40:509-19 pubmed publisher
    ..There were no changes in expression or phosphorylation of the bumetanide-sensitive cotransporter, NKCC2, or in expression of subunits of the amiloride-sensitive ion channel, ENaC...
  25. Tain Y, Lee W, Leu S, Wu K, Chan J. High salt exacerbates programmed hypertension in maternal fructose-fed male offspring. Nutr Metab Cardiovasc Dis. 2015;25:1146-51 pubmed publisher
    ..Better understanding of the effect of the relationship between HF and HS on hypertension development will help prevent hypertension in mothers and children exposed to HF and HS. ..
  26. Fujino S, Miyoshi N, Ohue M, Mukai M, Kukita Y, Hata T, et al. Rectal Cancer in a Patient with Bartter Syndrome: A Case Report. Genes (Basel). 2017;8: pubmed publisher
    ..We concluded that the tumor-related PGE2 elevation had worsened the patient's BS, which became more manageable after tumor resection. ..
  27. Udwan K, Abed A, Roth I, Dizin E, Maillard M, Bettoni C, et al. Dietary sodium induces a redistribution of the tubular metabolic workload. J Physiol. 2017;595:6905-6922 pubmed publisher
    ..As expected, LSD did not alter measured GFR and increased the abundance of total and cell-surface NHE3, NKCC2, NCC, α-ENaC and cleaved γ-ENaC compared to NSD...
  28. Bazúa Valenti S, Castañeda Bueno M, Gamba G. Physiological role of SLC12 family members in the kidney. Am J Physiol Renal Physiol. 2016;311:F131-44 pubmed publisher
    ..Most of these family members are expressed in specific regions of the nephron. The Na-K-2Cl cotransporter NKCC2, which is located in the thick ascending limb, and the Na-Cl cotransporter, which is located in the distal ..
  29. Wang L, Song J, Wang S, Buggs J, Chen R, Zhang J, et al. Cross-sex transplantation alters gene expression and enhances inflammatory response in the transplanted kidneys. Am J Physiol Renal Physiol. 2017;313:F326-F338 pubmed publisher
    ..of endothelin 1, endothelin ETA receptor, Na+-K--2Cl cotransporter 2 (NKCC2), and epithelial Na+ channels (ENaC) subunits exhibited decreases in M/F compared with M/M and ..
  30. Zhao J, Zhu X, Shrubsole M, Ness R, Hibler E, Cai Q, et al. Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study. Mol Carcinog. 2017;56:2258-2266 pubmed publisher
    ..These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer. ..
  31. Adragna N, Ravilla N, Lauf P, Begum G, Khanna A, Sun D, et al. Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis. Front Cell Neurosci. 2015;9:255 pubmed publisher
  32. Zhang J, Rudemiller N, Patel M, Karlovich N, Wu M, McDonough A, et al. Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron. Cell Metab. 2016;23:360-8 pubmed publisher
    ..deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron...
  33. Bachmann S, Mutig K. Regulation of renal Na-(K)-Cl cotransporters by vasopressin. Pflugers Arch. 2017;469:889-897 pubmed publisher
    ..convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT...
  34. Dong K, Yan Q, Lu M, Wan L, Hu H, Guo J, et al. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion. J Biol Chem. 2016;291:5259-69 pubmed publisher
    ..Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice...
  35. Lv J, Zhang D, Liu P, Li J. Effects of salinity acclimation and eyestalk ablation on Na(+), K(+), 2Cl(-) cotransporter gene expression in the gill of Portunus trituberculatus:a molecular correlate for salt-tolerant trait. Cell Stress Chaperones. 2016;21:829-36 pubmed publisher
    ..Our results indicate that PtNKCC plays an important role in the salinity acclimation of P. trituberculatus, while there may be a compound present in the XOSG that inhibits the expression of PtNKCC. ..
  36. Brandoni A, Torres A. Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy. Biomed Res Int. 2017;2017:7171928 pubmed publisher
    ..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...
  37. Zhang Y, Peti Peterdi J, Heiney K, Riquier Brison A, Carlson N, Müller C, et al. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice. Purinergic Signal. 2015;11:507-18 pubmed publisher
    ..immunoblotting revealed that CLPD alone increased renal aquaporin 2 (AQP2), Na-K-2Cl cotransporter (NKCC2), Na-Cl cotransporter (NCC), and the subunits of the epithelial Na channel (ENaC) in medulla by 25-130 %...
  38. Xu B, Tu D, Yan M, Shu M, Shao Q. Molecular characterization of a cDNA encoding Na+/K+/2Cl- cotransporter in the gill of mud crab (Scylla paramamosain) during the molt cycle: Implication of its function in osmoregulation. Comp Biochem Physiol A Mol Integr Physiol. 2017;203:115-125 pubmed publisher
    ..These data suggest that SpNKCC may be important in mediating branchial ion uptake during the molt cycle, especially at the postmolt stages. ..
  39. Esbaugh A, Cutler B. Intestinal Na+, K+, 2Cl- cotransporter 2 plays a crucial role in hyperosmotic transitions of a euryhaline teleost. Physiol Rep. 2016;4: pubmed
    ..increased expression of nkcc1 and cftr Expression changes in the anterior intestine were observed after 24 h for nkcc2 with smaller and later responses observed for slc26a3, slc26a6, and nbc Immunofluorescence staining demonstrated ..
  40. Song J, Wang L, Fan F, Wei J, Zhang J, Lu Y, et al. Role of the Primary Cilia on the Macula Densa and Thick Ascending Limbs in Regulation of Sodium Excretion and Hemodynamics. Hypertension. 2017;70:324-333 pubmed publisher
    ..A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-?/flox mice (NKCC2CRE; IFT88?/flox), in which the primary cilia were ..
  41. Bradford E, Vairamani K, Shull G. Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine. World J Gastrointest Pathophysiol. 2016;7:138-49 pubmed publisher
    ..The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors. ..
  42. Yang C, Kulkarni M, Lim M, Pak Y. In silico direct folding of thrombin-binding aptamer G-quadruplex at all-atom level. Nucleic Acids Res. 2017;: pubmed publisher
    ..s) parallel tempering metadynamics (PTMetaD) simulation method in conjunction with a modified version of the AMBER bsc1 force field...
  43. Borschewski A, Himmerkus N, Boldt C, Blankenstein K, McCormick J, Lazelle R, et al. Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate the Renal Na⁺-K⁺-2Cl⁻ Cotransporter. J Am Soc Nephrol. 2016;27:107-19 pubmed publisher
    The furosemide-sensitive Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) is crucial for NaCl reabsorption in kidney thick ascending limb (TAL) and drives the urine concentrating mechanism...
  44. Ramseyer V, Ortiz P, Carretero O, Garvin J. Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs. Am J Physiol Renal Physiol. 2016;310:F748-F754 pubmed publisher
    ..THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired...
  45. Xu W, Wang Y, Wu J, Li G. Quantitative analysis of U251MG human glioma cells invasion in organotypic brain slice co-cultures. Eur Rev Med Pharmacol Sci. 2016;20:2221-9 pubmed
    ..The OBSC model is a reliable and easy-to-perform in vitro method to quantify the glioma invasion ability. ..
  46. Wall S, Fischer M, Mehta P, Hassell K, Park S. Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. Am J Physiol Renal Physiol. 2001;280:F913-21 pubmed
    ..The physiological role of NKCC1-mediated Cl- uptake remains to be determined. However, the role of NKCC1 in the process of fluid secretion could not be demonstrated...
  47. Garg P, Martin C, Elms S, Gordon F, Wall S, Garland C, et al. Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol. 2007;292:H2100-5 pubmed
    ..We conclude that NKCC1 influences blood pressure through effects on smooth muscle tone in resistance vessels and that this effect is augmented in hypertension...
  48. Araujo M, Welch W, Zhou X, Sullivan K, Walsh S, Pasternak A, et al. Inhibition of ROMK blocks macula densa tubuloglomerular feedback yet causes renal vasoconstriction in anesthetized rats. Am J Physiol Renal Physiol. 2017;312:F1120-F1127 pubmed publisher
    The Na+-K+-2Cl- cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide...
  49. Aviv A, Hollenberg N, Weder A. Urinary potassium excretion and sodium sensitivity in blacks. Hypertension. 2004;43:707-13 pubmed
    ..In this sense, the biological implication of sodium sensitivity in blacks and in humans in general has ramifications above and beyond salt-evoked increase in blood pressure. ..
  50. Ji T, Liu S, Zheng L, Wang Q, Dou Z, Zhang Y, et al. Cellular distribution of NKCC2 in the gastric mucosa and its response to short-term osmotic shock. Cell Tissue Res. 2012;348:155-65 pubmed publisher
    The Na(+)-K(+)-2Cl(-) cotransporter-2 (NKCC2) has long been recognized as a "kidney-specific" transporter and is important in salt reabsorption...
  51. Ferdaus M, Barber K, López Cayuqueo K, Terker A, Argaiz E, Gassaway B, et al. SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule. J Physiol. 2016;594:4945-66 pubmed publisher
    ..stress-response kinase-1 (OSR1) phosphorylate and activate the renal Na(+) -K(+) -2Cl(-) cotransporter 2 (NKCC2) and Na(+) Cl(-) cotransporter (NCC)...
  52. Arion D, Lewis D. Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia. Arch Gen Psychiatry. 2011;68:21-31 pubmed publisher
  53. Asico L, Cuevas S, Ma X, Jose P, Armando I, Konkalmatt P. Nephron segment-specific gene expression using AAV vectors. Biochem Biophys Res Commun. 2018;497:19-24 pubmed publisher
    ..for expression in the S1 and S2 segments of the proximal tubule; sodium, potassium, 2 chloride co-transporter (NKCC2) gene promoter for expression in the thick ascending limb of Henle's loop (TALH); E-cadherin (ECAD) gene promoter ..
  54. Taylor C, Juang Y, Earnest S, Sengupta S, Goldsmith E, Cobb M. Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK. Biochemistry. 2015;54:5063-71 pubmed publisher
    ..The monomeric mutant is activated by WNK1 but has reduced activity toward its substrate NKCC2, suggesting regulatory roles for domain swapping...
  55. Liu G, Zhu T, Zhang A, Li F, Qian W, Qian B. Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. J Anesth. 2016;30:834-41 pubmed publisher
    ..These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. ..
  56. Zgarbová M, Jurecka P, Sponer J, Otyepka M. A- to B-DNA Transition in AMBER Force Fields and its Coupling to Sugar Pucker. J Chem Theory Comput. 2017;: pubmed publisher
    ..In this work, we examine the A/B equilibrium in three AMBER force fields, including the recent bsc1 and OL15 modifications, using much longer MD simulations than attempted before...
  57. Inokuchi M, Breves J, Moriyama S, Watanabe S, Kaneko T, Lerner D, et al. Prolactin 177, prolactin 188, and extracellular osmolality independently regulate the gene expression of ion transport effectors in gill of Mozambique tilapia. Am J Physiol Regul Integr Comp Physiol. 2015;309:R1251-63 pubmed publisher
    ..Together, these results provide evidence that ionocytes of Mozambique tilapia may function as osmoreceptors, as well as directly respond to PRL to modulate branchial ionoregulatory functions. ..
  58. Klein J, Wang Y, Blount M, Molina P, LaRocque L, Ruiz J, et al. Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts. Am J Physiol Renal Physiol. 2016;310:F1008-12 pubmed publisher
    ..monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM)...
  59. Richardson C, Sakamoto K, de los Heros P, Deak M, Campbell D, Prescott A, et al. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011;124:789-800 pubmed publisher
    ..Here, we study the regulation of the NKCC2 (SLC12A1) ion cotransporter that contributes towards ~25% of renal salt re-absorption and is inhibited by loop-..
  60. Rodriguez Soriano J. Bartter and related syndromes: the puzzle is almost solved. Pediatr Nephrol. 1998;12:315-27 pubmed
    ..defects have been identified: either at the gene encoding the renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP-sensitive inwardly rectifying K channel (ROMK)...
  61. Zhu J, Xue H, Ji T, Xing Y. Cellular localization of NKCC2 and its possible role in the Cl- absorption in the rat and human distal colonic epithelia. Transl Res. 2011;158:146-54 pubmed publisher
    Recently, we demonstrated the expression of NKCC2, an absorptive isoform of NKCC specifically expressed in the kidney, in the rat gastrointestinal tract including the distal colonic mucosa...
  62. Basta J, Robbins L, Denner D, Kolar G, Rauchman M. A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation. Development. 2017;144:3080-3094 pubmed publisher
    ..These global changes in gene expression were accompanied by a significant decrease in THP-, NKCC2- and AQP1-positive loop of Henle nephron segments in mutant ?SRM kidneys...
  63. Starremans P, Kersten F, Knoers N, van den Heuvel L, Bindels R. Mutations in the human Na-K-2Cl cotransporter (NKCC2) identified in Bartter syndrome type I consistently result in nonfunctional transporters. J Am Soc Nephrol. 2003;14:1419-26 pubmed
    ..These results are in line with the hypothesis that the mutations in hNKCC2 are the underlying cause of the clinical abnormalities seen in patients with type I BS...
  64. Nozu K, Iijima K, Kawai K, Nozu Y, Nishida A, Takeshima Y, et al. In vivo and in vitro splicing assay of SLC12A1 in an antenatal salt-losing tubulopathy patient with an intronic mutation. Hum Genet. 2009;126:533-8 pubmed publisher
    ..These analytical assays could be adapted for all inherited kidney diseases. ..
  65. Jensen J, Mose F, Kulik A, Bech J, Fenton R, Pedersen E. Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls. BMC Nephrol. 2014;15:101 pubmed publisher
    ..that abnormal activity of the aquaporin-2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contribute to this phenomenon...
  66. Layton A, Laghmani K, Vallon V, EDWARDS A. Solute transport and oxygen consumption along the nephrons: effects of Na+ transport inhibitors. Am J Physiol Renal Physiol. 2016;311:F1217-F1229 pubmed publisher
    ..exchanger (NHE3), the bumetanide-sensitive Na+-K+-2Cl- transporter (NKCC2), the Na+-Cl- cotransporter (NCC), and the amiloride-sensitive Na+ channel (ENaC)...
  67. Moreno E, Gayosso J, Montejano J, Almaguer G, Vazquez N, Cruz C, et al. Geraniin is a diuretic by inhibiting the Na+:K+:2Cl- cotransporter, NKCC2. Am J Physiol Renal Physiol. 2017;:ajprenal.00221.2017 pubmed publisher
    ..laevis oocytes were microinjected with cRNAs encoding the Na-Cl cotransporter (NCC) and the Na-K-2Cl cotransporter NKCC2 to functionally express these cotransporters...
  68. Nasrallah R, Zimpelmann J, Eckert D, Ghossein J, Geddes S, Beique J, et al. PGE2 EP1 receptor inhibits vasopressin-dependent water reabsorption and sodium transport in mouse collecting duct. Lab Invest. 2017;: pubmed publisher
    ..Thick ascending limb NKCC2 was reduced in the cortex but increased in the medulla...
  69. Igarashi P, Vanden Heuvel G, Payne J, Forbush B. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol. 1995;269:F405-18 pubmed
    A full-length cDNA encoding the murine renal Na-K-Cl cotransporter (NKCC2) was cloned using library screening and anchored polymerase chain reaction. The deduced protein sequence contained 1,095 amino acids and was 93...
  70. Haas M, Forbush B. The Na-K-Cl cotransporters. J Bioenerg Biomembr. 1998;30:161-72 pubmed
    ..By contrast, NKCC2 (CCC2, BSC1) is found only in the kidney, localized to the apical membrane of the epithelial cells of the thick ..
  71. Lindinger M, Grudzien S. Exercise-induced changes in plasma composition increase erythrocyte Na+,K+-ATPase, but not Na+-K+-2Cl- cotransporter, activity to stimulate net and unidirectional K+ transport in humans. J Physiol. 2003;553:987-97 pubmed
    ..It is concluded that RBCs rapidly increase JK,in and JK,net in response to exercise-induced changes in plasma composition. ..
  72. Ernandez T, Udwan K, Chassot A, Martin P, Feraille E. Uninephrectomy and apical fluid shear stress decrease ENaC abundance in collecting duct principal cells. Am J Physiol Renal Physiol. 2017;:ajprenal.00200.2017 pubmed publisher
    ..uninephrectomy, while the expression of the aldosterone-sensitive ?-ENaC and ?1-Na,K-ATPase subunits as well as of NKCC2 and NCC were not significantly altered...
  73. Zhuang Y, Jia Z, Hu C, Ding G, Zhang X, Zhang Y, et al. Albuminuria confers renal resistance to loop diuretics via the stimulation of NLRP3 inflammasome/prostaglandin signaling in thick ascending limb. Oncotarget. 2017;8:75808-75821 pubmed publisher
    ..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...
  74. Russell J. Sodium-potassium-chloride cotransport. Physiol Rev. 2000;80:211-76 pubmed
    ..One isoform (NKCC2) has at least three alternatively spliced variants and is found exclusively in the kidney...
  75. Grubb B, Lee E, Pace A, Koller B, Boucher R. Intestinal ion transport in NKCC1-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2000;279:G707-18 pubmed
  76. Iwai N, Tago N, Yasui N, Kokubo Y, Inamoto N, Tomoike H, et al. Genetic analysis of 22 candidate genes for hypertension in the Japanese population. J Hypertens. 2004;22:1119-26 pubmed
    ..967, 95% confidence interval = 1.430-2.712). Although the present results should be replicated in other study populations for confirmation, the present results suggest that SLC12A1 may contribute to hypertension in Japanese women. ..
  77. Vormfelde S, Sehrt D, Toliat M, Schirmer M, Meineke I, Tzvetkov M, et al. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007;82:300-9 pubmed
    ..in a crossover study in 97 healthy Caucasians in relation to genetic variation in the renal sodium transporters NKCC2 (coded by SLC12A1), NCC (SLC12A3), and ENaC (three subunits coded by SCNN1A, SCNN1B, and SCNN1G)...
  78. Breinbjerg A, Siggaard Rittig C, Gregersen N, Rittig S, Hvarregaard Christensen J. A novel variant in the SLC12A1 gene in two families with antenatal Bartter syndrome. Acta Paediatr. 2017;106:161-167 pubmed publisher
    ..This could eventually be explained by the presence of other gene variants or environmental factors modifying the phenotypes. The phenotypes of the patients were similar to other patients with antenatal Bartter syndrome. ..
  79. Yerby T, Vibat C, Sun D, Payne J, O Donnell M. Molecular characterization of the Na-K-Cl cotransporter of bovine aortic endothelial cells. Am J Physiol. 1997;273:C188-97 pubmed
    ..have been identified, the cotransporter in secretory epithelia, NKCC1, and that in absorptive renal epithelia, NKCC2. Our previous studies showed that a monoclonal antibody to the cotransporter of human colonic T84 epithelial cells,..
  80. Adachi M, Asakura Y, Sato Y, Tajima T, Nakajima T, Yamamoto T, et al. Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. Endocr J. 2007;54:1003-7 pubmed
    ..BS type 1 is caused by mutations in the SLC12A1 gene encoding bumetanide-sensitive Na-K-2Cl (-) cotransporter (NKCC2)...
  81. Zhang Y, Li Y, Qiu F, Qiu Z. Comprehensive analysis of low-abundance proteins in human urinary exosomes using peptide ligand library technology, peptide OFFGEL fractionation and nanoHPLC-chip-MS/MS. Electrophoresis. 2010;31:3797-807 pubmed publisher
    ..Our work also provides an effective strategy of concentration and identification of low-abundance proteome from complex bio-samples. ..
  82. Daga A, Majmundar A, Braun D, Gee H, Lawson J, Shril S, et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 2018;93:204-213 pubmed publisher
    ..Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years. ..
  83. Jalali R, Lodder J, Zandieh Doulabi B, Micha D, Melvin J, Catalán M, et al. The Role of Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) in Dental Epithelium during Enamel Formation in Mice. Front Physiol. 2017;8:924 pubmed publisher
    ..The increased amount of Cx43 in enamel organ cells in Nkcc1-null mice suggests that these cells display a higher number of gap junctions to increase intercellular communication...
  84. Jung J, Sun B, Kwon D, Koller D, Foroud T. Allelic-based gene-gene interaction associated with quantitative traits. Genet Epidemiol. 2009;33:332-43 pubmed publisher
  85. Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher M, et al. Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome. Nephrol Dial Transplant. 2009;24:1455-64 pubmed publisher
    ..Chronic renal failure is a rare event, associated in this cohort with three genotypes and not always associated with nephrocalcinosis. ..
  86. Puricelli E, Bettinelli A, Borsa N, Sironi F, Mattiello C, Tammaro F, et al. Long-term follow-up of patients with Bartter syndrome type I and II. Nephrol Dial Transplant. 2010;25:2976-81 pubmed publisher
    ..Little information is available on a long-term follow-up in Bartter syndrome type I and II...
  87. Castrop H, Schnermann J. Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance. Am J Physiol Renal Physiol. 2008;295:F859-66 pubmed publisher
    The renal Na-K-2Cl cotransporter (NKCC2, BSC1) is selectively expressed in the apical membrane of cells of the thick ascending limb of the loop of Henle (TAL) and macula densa...
  88. Urbanova M, Reiterova J, Stekrova J, Lnenicka P, Rysava R. DNA analysis of renal electrolyte transporter genes among patients suffering from Bartter and Gitelman syndromes: summary of mutation screening. Folia Biol (Praha). 2011;57:65-73 pubmed
    ..Nine of these mutations are novel. In one case, genetic analysis led to re-evaluation of diagnosis between the Gitelman and classic form of Bartter syndrome. ..
  89. Gagnon K, Delpire E. Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts. Am J Physiol Cell Physiol. 2013;304:C693-714 pubmed publisher
  90. Kurtz C, Karolyi L, Seyberth H, Koch M, Vargas R, Feldmann D, et al. A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect. J Am Soc Nephrol. 1997;8:1706-11 pubmed
    ..In these patients, mutations in the genes encoding either the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the ATP-regulated potassium channel ROMK (KCNJI) have been identified...
  91. Monette M, Rinehart J, Lifton R, Forbush B. Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function. Am J Physiol Renal Physiol. 2011;300:F840-7 pubmed publisher
    The Na-K-Cl cotransporter (NKCC2) is the major salt transport pathway in the thick ascending limb of Henle's loop and is part of the molecular mechanism for blood pressure regulation...
  92. Petrezselyova S, Dominguez A, Herynkova P, Macias J, Sychrova H. Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes. Yeast. 2013;30:395-402 pubmed
    ..In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of ..