| http://purl.uniprot.org/citations/15902302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15902302 | http://www.w3.org/2000/01/rdf-schema#comment | "Thiazide diuretics enhance renal Na+ excretion by blocking the Na+-Cl-cotransporter (NCC), and mutations in NCC result in Gitelman syndrome. The mechanisms underlying the accompanying hypocalciuria and hypomagnesemia remain debated. Here, we show that enhanced passive Ca2+ transport in the proximal tubule rather than active Ca2+ transport in distal convolution explains thiazide-induced hypocalciuria. First, micropuncture experiments in mice demonstrated increased reabsorption of Na+ and Ca2+ in the proximal tubule during chronic hydrochlorothiazide (HCTZ) treatment, whereas Ca2+ reabsorption in distal convolution appeared unaffected. Second, HCTZ administration still induced hypocalciuria in transient receptor potential channel subfamily V, member 5-knockout (Trpv5-knockout) mice, in which active distal Ca2+ reabsorption is abolished due to inactivation of the epithelial Ca2+ channel Trpv5. Third, HCTZ upregulated the Na+/H+ exchanger, responsible for the majority of Na+ and, consequently, Ca2+ reabsorption in the proximal tubule, while the expression of proteins involved in active Ca2+ transport was unaltered. Fourth, experiments addressing the time-dependent effect of a single dose of HCTZ showed that the development of hypocalciuria parallels a compensatory increase in Na+ reabsorption secondary to an initial natriuresis. Hypomagnesemia developed during chronic HCTZ administration and in NCC-knockout mice, an animal model of Gitelman syndrome, accompanied by downregulation of the epithelial Mg2+ channel transient receptor potential channel subfamily M, member 6 (Trpm6). Thus, Trpm6 downregulation may represent a general mechanism involved in the pathogenesis of hypomagnesemia accompanying NCC inhibition or inactivation."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci24134"xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "Loffing J."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "Vallon V."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "Bindels R.J."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "Hoenderop J.G."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "van der Kemp A.W."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/author | "Nijenhuis T."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/pages | "1651-1658"xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/title | "Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia."xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://purl.uniprot.org/core/volume | "115"xsd:string |
| http://purl.uniprot.org/citations/15902302 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15902302 |
| http://purl.uniprot.org/citations/15902302 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15902302 |
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| http://purl.uniprot.org/uniprot/#_P59158-mappedCitation-15902302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15902302 |
| http://purl.uniprot.org/uniprot/#_Q62439-mappedCitation-15902302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15902302 |
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