RGD Reference Report - Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2. - Rat Genome Database

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Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2.

Authors: Kurata, T  Muraki, Y  Mizutani, H  Iwamoto, T  Okuda, M 
Citation: Kurata T, etal., Drug Metab Pharmacokinet. 2010;25(4):328-34.
RGD ID: 7243879
Pubmed: PMID:20814153   (View Abstract at PubMed)

Renal tubular secretion of cationic drugs is dominated by two classes of organic cation transporters, OCT2/SLC22A2 and MATE1/SLC47A1, localized to the basolateral and brush-border membranes of the renal tubular epithelial cells, respectively. However, little is known about the expression and function of these transporters in acute cholestasis. Systemic clearance of cimetidine was significantly higher in rats with bile duct ligation (BDL) for 24 hours than in sham-operated rats, with no significant changes in the volume of distribution between the groups. In addition, net tubular secretory clearance of cimetidine was significantly higher in the BDL rats compared with the sham rats, with no significant changes in the glomerular filtration rate. Moreover, the renal tissue-to-plasma concentration ratio of cimetidine was elevated in BDL rats, although the renal tissue-to-urine clearance ratio of cimetidine was not different between the two groups. The expression level of basolateral organic cation transporter rOCT2 protein in the kidney cortex was markedly higher in BDL rats than that in the sham rats, but that of H+/organic cation antiporter rMATE1 protein in the brush-border membranes was not significantly different between the two groups. These results demonstrate that the renal tubular secretion of cimetidine was increased by acute cholestasis, and this increase was attributable to elevated expression levels of rOCT2 but not of rMATE1 in the rat.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extrahepatic cholestasis  ISOSlc22a1 (Rattus norvegicus)7243879; 7243879protein:decreased expression:kidneyRGD 
extrahepatic cholestasis  ISOSlc22a2 (Rattus norvegicus)7243879; 7243879protein:increased expression:kidneyRGD 
extrahepatic cholestasis  IEP 7243879protein:decreased expression:kidneyRGD 
extrahepatic cholestasis  IEP 7243879protein:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc22a1  (solute carrier family 22 member 1)
Slc22a2  (solute carrier family 22 member 2)

Genes (Mus musculus)
Slc22a1  (solute carrier family 22 (organic cation transporter), member 1)
Slc22a2  (solute carrier family 22 (organic cation transporter), member 2)

Genes (Homo sapiens)
SLC22A1  (solute carrier family 22 member 1)
SLC22A2  (solute carrier family 22 member 2)


Additional Information