RGD Reference Report - Down-regulation of rat organic cation transporter rOCT2 by 5/6 nephrectomy. - Rat Genome Database

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Down-regulation of rat organic cation transporter rOCT2 by 5/6 nephrectomy.

Authors: Ji, L  Masuda, S  Saito, H  Inui, K 
Citation: Ji L, etal., Kidney Int. 2002 Aug;62(2):514-24.
RGD ID: 7243883
Pubmed: PMID:12110012   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1523-1755.2002.00464.x   (Journal Full-text)

BACKGROUND: In rat kidneys, the organic ion transporters rOCT1, rOCT2, rOAT1 and rOAT3 are considered to mediate the basolateral uptake of various ionic compounds. However, their changes in chronic renal failure (CRF) are poorly understood. The present study examined the renal handling of organic ions and the expression of these transporters under CRF. METHODS: 5/6 Nephrectomized rats were used as the animal model of CRF. Renal handlings of cimetidine and paraaminohippuric acid (PAH) were examined by in vivo experiments. rOAT1, rOAT3, rOCT1 and rOCT2 expressions were determined by Western blotting. RESULTS: The tubular secretion rates of both PAH and cimetidine were markedly decreased in CRF rats. Although the distribution rates of PAH into the kidney cortex and medulla, and of cimetidine into the kidney cortex were maintained, the distribution rate of cimetidine into the kidney medulla was significantly decreased in CRF rats. The expression level of the rOCT2 protein was markedly depressed in CRF rats, but those of rOCT1, rOAT1 and rOAT3 were maintained. In addition, the plasma concentration of testosterone, a regulator of rOCT2 expression, was significantly reduced by CRF. Both the renal clearance of cimetidine and rOCT2 expression were recovered by the exogenous administration of testosterone in CRF rats. CONCLUSIONS: The levels of urinary excretion of cationic drugs, especially substrates for rOCT2, were reduced under CRF partly due to the reduced expression of rOCT2, and the lowered plasma level of testosterone was suggested to be responsible for the depressed rOCT2 expression in CRF.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC22A2Humanend stage renal disease  ISOSlc22a2 (Rattus norvegicus)protein:decreased expression:kidney and plasma membraneRGD 
Slc22a2Ratend stage renal disease  IEP protein:decreased expression:kidney and plasma membraneRGD 
Slc22a2Mouseend stage renal disease  ISOSlc22a2 (Rattus norvegicus)protein:decreased expression:kidney and plasma membraneRGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc22a2  (solute carrier family 22 member 2)

Genes (Mus musculus)
Slc22a2  (solute carrier family 22 (organic cation transporter), member 2)

Genes (Homo sapiens)
SLC22A2  (solute carrier family 22 member 2)


Additional Information