Linked Life Data

21429969

Source:http://linkedlifedata.com/resource/pubmed/id/21429969

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-7-7
pubmed:abstractText
N-methyl-D-aspartate receptors (NMDARs) are Ca(2+)-permeable, ligand-gated, nonselective cation channels that function as neuronal synaptic receptors but which are also expressed in multiple peripheral tissues. Here, we show for the first time that NMDAR subunits NR3a and NR3b are highly expressed in the neonatal kidney and that there is continued expression of NR3a in the renal medulla and papilla of the adult mouse. NR3a was also expressed in mIMCD-3 cells, where it was found that hypoxia and hypertonicity upregulated NR3a expression. Using short-hairpin (sh) RNA-based knockdown, a stable inner medullary collecting duct (IMCD) cell line was established that had ?80% decrease in NR3a. Knockdown cells exhibited an increased basal intracellular calcium concentration, reduced cell proliferation, and increased cell death. In addition, NR3a knockdown cells exhibited reduced water transport in response to the addition of vasopressin, suggesting an alteration in aquaporin-2 (AQP2) expression/function. Consistent with this notion, we demonstrate decreased surface expression of glycosylated AQP2 in IMCD cells transfected with NR3a shRNA. To determine whether this also occurred in vivo, we compared AQP2 levels in wild-type vs. in NR3a(-/-) mice. Total AQP2 protein levels in the outer and inner medulla were significantly reduced in knockout mice compared with control mice. Finally, NR3a(-/-) mice showed a significant delay in their ability to increase urine osmolality during water restriction. Thus NR3a may play a renoprotective role in collecting duct cells. Therefore, under conditions that are associated with high vasopressin levels, NR3a, by maintaining low intracellular calcium levels, protects the function of the principal cells to reabsorb water and thereby increase medullary osmolality.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F44-54
pubmed:meshHeading
pubmed-meshheading:21429969-Animals, pubmed-meshheading:21429969-Aquaporin 2, pubmed-meshheading:21429969-Blotting, Western, pubmed-meshheading:21429969-Calcium, pubmed-meshheading:21429969-Calcium Signaling, pubmed-meshheading:21429969-Cells, Cultured, pubmed-meshheading:21429969-Humans, pubmed-meshheading:21429969-Hypertonic Solutions, pubmed-meshheading:21429969-Immunohistochemistry, pubmed-meshheading:21429969-Kidney Concentrating Ability, pubmed-meshheading:21429969-Kidney Medulla, pubmed-meshheading:21429969-Kidney Tubules, Collecting, pubmed-meshheading:21429969-Membrane Proteins, pubmed-meshheading:21429969-Mice, pubmed-meshheading:21429969-Mice, Knockout, pubmed-meshheading:21429969-Osmolar Concentration, pubmed-meshheading:21429969-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:21429969-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21429969-Serine, pubmed-meshheading:21429969-Transcription Factors, pubmed-meshheading:21429969-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct.
pubmed:affiliation
Department of Medicine, Medical University of South Carolina, Charleston, SC 29403, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural