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Book ; Online ; Thesis: Bedeutung der Interaktion von Calcineurin und SORLA für die Regulation des Na+, K+, 2CI--Kotransporters (NKCC2) in der Niere

Borschewski, Aljona / Bachmann, Sebastian / Gräf, Ralph

2016

Abstract: Der Na⁺-K⁺-2Cl⁻-Kotransporter (NKCC2) wird im distalen Nephron der Niere exprimiert. Seine Verteilung umfasst die Epithelien der medullären und kortikalen Teile der dicken aufsteigenden Henle-Schleife (Thick ascending limb, TAL) und die Macula densa. ... ...

Title variant	Importance of the interaction between calcineurin and SORLA for the regulation of the renal Na+-K+-2CI--cotransporter (NKCC2)
Author's details	vorgelegt von Aljona Borschewski
Abstract	Der Na⁺-K⁺-2Cl⁻-Kotransporter (NKCC2) wird im distalen Nephron der Niere exprimiert. Seine Verteilung umfasst die Epithelien der medullären und kortikalen Teile der dicken aufsteigenden Henle-Schleife (Thick ascending limb, TAL) und die Macula densa. Resorptiver NaCl-Transport über den NKCC2 dient dem renalen Konzentrierungsmechanismus und reguliert systemisch auch Volumenstatus und Blutdruck. Die Aktivität des NKCC2 ist mit der Phosphorylierung seiner N-terminalen Aminosäurereste Serin 126 und Threonin 96/101 verbunden. Vermittelt wird diese durch die homologen Kinasen SPAK (SPS-related proline/alanine-rich kinase) und OSR1 (Oxidative stress responsive kinase 1), die hierzu ihrerseits phosphoryliert werden müssen. Der regulatorische Kontext dieser Kinasen ist mittlerweile gut charakterisiert. Über Mechanismen und Produkte, die den NKCC2 deaktivieren, war hingegen weniger bekannt. Ziel der Arbeit war daher zu untersuchen, welche Wege zur Deaktivierung des Transporters führen. Der intrazelluläre Sortierungsrezeptor SORLA (Sorting-prote…
Language	German
Size	1 Online-Ressource (II, 86 Blätter), Illustrationen, Diagramme
Publishing place	Potsdam
Publishing country	Germany
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Dissertation, Universität Potsdam, Mathematisch-Naturwissenschaftliche Fakultät, 2016
HBZ-ID	HT019856231
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Caveolin 1 Promotes Renal Water and Salt Reabsorption.

Willière, Yan / Borschewski, Aljona / Patzak, Andreas / Nikitina, Tatiana / Dittmayer, Carsten / Daigeler, Anna L / Schuelke, Markus / Bachmann, Sebastian / Mutig, Kerim

Scientific reports

2018 Volume 8, Issue 1, Page(s) 545

Abstract: Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1-/-) mice ... ...

Abstract	Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1-/-) mice were studied. Cav1 expression and caveolae formation were present in vascular cells, late distal convoluted tubule and principal connecting tubule and collecting duct cells of WT but not Cav1-/- kidneys. Urinary sodium excretion was increased by 94% and urine flow by 126% in Cav1-/- mice (p < 0.05). A decrease in activating phosphorylation of the Na-Cl cotransporter (NCC) of the distal convoluted tubule was recorded in Cav1-/- compared to WT kidneys (-40%; p < 0.05). Isolated intrarenal arteries from Cav1-/- mice revealed a fourfold reduction in sensitivity to phenylephrine (p < 0.05). A significantly diminished maximal contractile response (-13%; p < 0.05) was suggestive of enhanced nitric oxide (NO) availability. In line with this, the abundance of endothelial NO synthase (eNOS) was increased in Cav1-/- kidneys +213%; p < 0.05) and cultured caveolae-deprived cells showed intracellular accumulation of eNOS, compared to caveolae-intact controls. Our results suggest that renal caveolae help to conserve water and electrolytes via modulation of NCC function and regulation of vascular eNOS.
MeSH term(s)	Animals ; Caveolin 1/genetics ; Caveolin 1/metabolism ; Cells, Cultured ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiology ; Humans ; Kidney/blood supply ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Renal Artery/metabolism ; Renal Artery/physiology ; Renal Reabsorption ; Sodium/metabolism ; Sodium-Calcium Exchanger/metabolism
Chemical Substances	Cav1 protein, mouse ; Caveolin 1 ; Sodium-Calcium Exchanger ; Nitric Oxide (31C4KY9ESH) ; Sodium (9NEZ333N27) ; Nitric Oxide Synthase Type III (EC 1.14.13.39)
Language	English
Publishing date	2018-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-19071-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online ; Thesis: Bedeutung der Interaktion von Calcineurin und SORLA für die Regulation des Na⁺,K⁺,2Cl⁻-Kotransporters (NKCC2) in der Niere

Borschewski, Aljona [Verfasser] / Bachmann, Sebastian [Akademischer Betreuer] / Gräf, Ralph [Akademischer Betreuer]

2015

Author's details	Aljona Borschewski ; Sebastian Bachmann, Ralph Gräf
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	German
Publisher	Universität Potsdam
Publishing place	Potsdam
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Caveolin 1 Promotes Renal Water and Salt Reabsorption

Yan Willière / Aljona Borschewski / Andreas Patzak / Tatiana Nikitina / Carsten Dittmayer / Anna L. Daigeler / Markus Schuelke / Sebastian Bachmann / Kerim Mutig

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 14

Abstract: Abstract Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1−/− ...

Abstract	Abstract Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1−/−) mice were studied. Cav1 expression and caveolae formation were present in vascular cells, late distal convoluted tubule and principal connecting tubule and collecting duct cells of WT but not Cav1−/− kidneys. Urinary sodium excretion was increased by 94% and urine flow by 126% in Cav1−/− mice (p < 0.05). A decrease in activating phosphorylation of the Na-Cl cotransporter (NCC) of the distal convoluted tubule was recorded in Cav1−/− compared to WT kidneys (−40%; p < 0.05). Isolated intrarenal arteries from Cav1−/− mice revealed a fourfold reduction in sensitivity to phenylephrine (p < 0.05). A significantly diminished maximal contractile response (−13%; p < 0.05) was suggestive of enhanced nitric oxide (NO) availability. In line with this, the abundance of endothelial NO synthase (eNOS) was increased in Cav1−/− kidneys +213%; p < 0.05) and cultured caveolae-deprived cells showed intracellular accumulation of eNOS, compared to caveolae-intact controls. Our results suggest that renal caveolae help to conserve water and electrolytes via modulation of NCC function and regulation of vascular eNOS.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach.

Mutig, Kerim / Borowski, Tordis / Boldt, Christin / Borschewski, Aljona / Paliege, Alexander / Popova, Elena / Bader, Michael / Bachmann, Sebastian

American journal of physiology. Renal physiology

2016 Volume 311, Issue 2, Page(s) F411–23

Abstract: 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 ... ...

Abstract	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. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242stop) was then introduced into the rat genome under control of the Tamm-Horsfall protein promoter to cause a tissue-specific AVP-signaling defect exclusively in TAL. Resulting Ni3-V2R transgenic rats revealed decreased basolateral but increased intracellular V2R signal in TAL epithelia, suggesting impaired trafficking of the receptor. Rats displayed significant baseline polyuria, failure to concentrate the urine in response to water deprivation, and hypercalciuria. NKCC2 abundance, phosphorylation, and surface expression were markedly decreased. In summary, these data indicate that suppression of AVP-V2R signaling in TAL causes major impairment in renal fluid and electrolyte handling. Our results may have clinical implications.
MeSH term(s)	Animals ; Carrier Proteins/metabolism ; Cyclic AMP/metabolism ; Cyclooxygenase 2/metabolism ; Diabetes Insipidus, Nephrogenic/genetics ; Epithelium/metabolism ; Genetic Diseases, X-Linked/genetics ; Juxtaglomerular Apparatus/metabolism ; Kidney/physiology ; Kidney/ultrastructure ; Kidney Cortex/metabolism ; Kidney Medulla/metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; Receptors, Vasopressin/genetics ; Signal Transduction/genetics ; Signal Transduction/physiology ; Solute Carrier Family 12, Member 1/genetics ; Solute Carrier Family 12, Member 1/metabolism ; Vasopressins/genetics ; Vasopressins/physiology
Chemical Substances	Carrier Proteins ; Receptors, Vasopressin ; Slc12a1 protein, rat ; Solute Carrier Family 12, Member 1 ; V2 vasopressin receptor, rat ; Vasopressins (11000-17-2) ; Cyclic AMP (E0399OZS9N) ; Cyclooxygenase 2 (EC 1.14.99.1)
Language	English
Publishing date	2016-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00126.2016
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Article ; Online: Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

Thiele, Sonja / Borschewski, Aljona / Küchler, Judit / Bieberbach, Marc / Voigt, Sebastian / Ehlers, Bernhard

Clinical and vaccine immunology : CVI

2011 Volume 18, Issue 7, Page(s) 1058–1066

Abstract: To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and ...

Abstract	To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.
MeSH term(s)	Animals ; Chickenpox Vaccine/adverse effects ; Child ; DNA, Viral/genetics ; Exanthema/etiology ; Exanthema/virology ; Herpesvirus 3, Human/genetics ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Skin Diseases/etiology ; Skin Diseases/virology
Chemical Substances	Chickenpox Vaccine ; DNA, Viral
Language	English
Publishing date	2011-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2221082-9
ISSN	1556-679X ; 1556-6811
ISSN (online)	1556-679X
ISSN	1556-6811
DOI	10.1128/CVI.05021-11
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Article ; Online: Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate the Renal Na⁺-K⁺-2Cl⁻ Cotransporter.

Borschewski, Aljona / Himmerkus, Nina / Boldt, Christin / Blankenstein, Katharina I / McCormick, James A / Lazelle, Rebecca / Willnow, Thomas E / Jankowski, Vera / Plain, Allein / Bleich, Markus / Ellison, David H / Bachmann, Sebastian / Mutig, Kerim

Journal of the American Society of Nephrology : JASN

2016 Volume 27, Issue 1, Page(s) 107–119

Abstract: 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. NKCC2 activity is modulated by N-terminal phosphorylation and ... ...

Abstract	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. NKCC2 activity is modulated by N-terminal phosphorylation and dephosphorylation. Serine-threonine kinases that activate NKCC2 have been identified, but less is known about phosphatases that deactivate NKCC2. Inhibition of calcineurin phosphatase has been shown to stimulate transport in the TAL and the distal convoluted tubule. Here, we identified NKCC2 as a target of the calcineurin Aβ isoform. Short-term cyclosporine administration in mice augmented the abundance of phospho-NKCC2, and treatment of isolated TAL with cyclosporine increased the chloride affinity and transport activity of NKCC2. Because sorting-related receptor with A-type repeats (SORLA) may affect NKCC2 phosphoregulation, we used SORLA-knockout mice to test whether SORLA is involved in calcineurin-dependent modulation of NKCC2. SORLA-deficient mice showed more calcineurin Aβ in the apical region of TAL cells and less NKCC2 phosphorylation and activity compared with littermate controls. In contrast, overexpression of SORLA in cultured cells reduced the abundance of endogenous calcineurin Aβ. Cyclosporine administration rapidly normalized the abundance of phospho-NKCC2 in SORLA-deficient mice, and a functional interaction between calcineurin Aβ and SORLA was further corroborated by binding assays in rat kidney extracts. In summary, we have shown that calcineurin Aβ and SORLA are key components in the phosphoregulation of NKCC2. These results may have clinical implications for immunosuppressive therapy using calcineurin inhibitors.
MeSH term(s)	Animals ; Calcineurin/physiology ; Kidney/metabolism ; Male ; Membrane Transport Proteins/physiology ; Mice ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptors, LDL/physiology ; Sodium-Potassium-Chloride Symporters/physiology
Chemical Substances	Membrane Transport Proteins ; Receptors, LDL ; Sodium-Potassium-Chloride Symporters ; Sorl1 protein, mouse ; Calcineurin (EC 3.1.3.16) ; PPP3CB protein, human (EC 3.1.3.16)
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2014070728
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Article ; Online: Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

Thiele, Sonja / Borschewski, Aljona / Küchler, Judit / Bieberbach, Marc / Voigt, Sebastian / Ehlers, Bernhard

2011

Abstract	To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.
Keywords	Medizin ; Animals ; Humans ; Child ; Sequence Analysis DNA ; DNA Viral/genetics ; Chickenpox Vaccine/adverse effects ; Exanthema/etiology ; Exanthema/virology ; Herpesvirus 3 Human/genetics ; Polymorphism Single Nucleotide ; Skin Diseases/etiology ; Skin Diseases/virology ; ddc:610
Subject code	630
Language	English
Publishing date	2011-05-11
Publisher	Infektionskrankheiten / Erreger
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

Thiele, Sonja / Borschewski, Aljona / Küchler, Judit / Bieberbach, Marc / Voigt, Sebastian / Ehlers, Bernhard

2011

Abstract	To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.
Keywords	Animals ; Humans ; Child ; Sequence Analysis DNA ; DNA Viral/genetics ; Chickenpox Vaccine/adverse effects ; Exanthema/etiology ; Exanthema/virology ; Herpesvirus 3 Human/genetics ; Polymorphism Single Nucleotide ; Skin Diseases/etiology ; Skin Diseases/virology ; 610 Medizin ; ddc:610
Language	English
Publishing date	2011-05-11
Publisher	Robert Koch-Institut, Infektionskrankheiten / Erreger
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SPAK differentially mediates vasopressin effects on sodium cotransporters.

Saritas, Turgay / Borschewski, Aljona / McCormick, James A / Paliege, Alexander / Dathe, Christin / Uchida, Shinichi / Terker, Andrew / Himmerkus, Nina / Bleich, Markus / Demaretz, Sylvie / Laghmani, Kamel / Delpire, Eric / Ellison, David H / Bachmann, Sebastian / Mutig, Kerim

Journal of the American Society of Nephrology : JASN

2013 Volume 24, Issue 3, Page(s) 407–418

Abstract: Activation of the Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) and the Na(+)-Cl(-)-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this ... ...

Abstract	Activation of the Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) and the Na(+)-Cl(-)-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor-specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron.
MeSH term(s)	Animals ; Deamino Arginine Vasopressin/pharmacology ; Enzyme Activation/drug effects ; Kidney/drug effects ; Kidney/metabolism ; Male ; Mice ; Mice, Knockout ; Phosphorylation ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/deficiency ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Rats ; Rats, Brattleboro ; Receptors, Vasopressin/agonists ; Sodium Chloride Symporters/metabolism ; Sodium-Potassium-Chloride Symporters/metabolism ; Solute Carrier Family 12, Member 1
Chemical Substances	Receptors, Vasopressin ; Slc12a1 protein, mouse ; Slc12a1 protein, rat ; Sodium Chloride Symporters ; Sodium-Potassium-Chloride Symporters ; Solute Carrier Family 12, Member 1 ; Protein Kinases (EC 2.7.-) ; Stk39 protein, mouse (EC 2.7.1.-) ; PAS domain kinases (EC 2.7.1.11) ; OXSR1 protein, mouse (EC 2.7.11.1) ; Oxsr1 protein, rat (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2013-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2012040404
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