| Molecular Regulation of NKCC2 in the Thick Ascending Limb. | |
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MedLine Citation:
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PMID: 21900458 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The kidney plays an essential role in blood pressure regulation by controlling short-term and long-term NaCl and water balance. The thick ascending limb of the loop of Henle (THAL) reabsorbs 25-30% of the NaCl filtered by the glomeruli in a process mediated by the apical Na(+)/K(+)/2Cl- cotransporter NKCC2, which allows Na(+) and Cl(-) entry from the tubule lumen into THAL cells. In humans, mutations in the gene coding for NKCC2 result in decreased or absent activity characterized by severe salt and volume loss and decreased blood pressure (Bartter syndrome type 1). Opposite to Bartter's syndrome, enhanced NaCl absorption by the THAL is associated to human hypertension and animal models of salt-sensitive hypertension. THAL NaCl reabsoption is subject to exquisite control by hormones like vasopressin, parathyroid, glucagon, and adrenergic agonists (epinephrine and norepinephrine) that stimulate NaCl reabsorption. Atrial natriuretic peptides or autacoids like NO and prostaglandins inhibit NaCl reabsorption, promoting salt excretion. In general, the mechanism by which hormones control NaCl reabsorption is mediated directly or indirectly by altering the activity of NKCC2 in the THAL. Despite the importance of NKCC2 in renal physiology the molecular mechanisms by which hormones, autacoids, physical factors, and intracellular ions regulate NKCC2 activity are largely unknown. During the last 5 years it has become apparent that at least three molecular mechanisms determine NKCC2 activity. As such membrane trafficking, phosphorylation, and protein-protein interactions have recently been described in THALs and heterologous expression systems as mechanisms that modulate NKCC2 activity. The focus of this review is to summarize recent data regarding NKCC2 regulation and discuss their potential implications in physiological control of THAL function, renal physiology, and blood pressure regulation. |
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Authors:
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Gustavo R Ares; Paulo S Caceres; Pablo A Ortiz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-7 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: - ISSN: 1522-1466 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Henry Ford Hospital. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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