|
KMID : 0043320120350081441
|
|
Archives of Pharmacal Research
2012 Volume.35 No. 8 p.1441 ~ p.1448
|
|
|
Differential changes in functional activity of organic cation transporters in rats with uranyl nitrate-induced acute renal failure
|
|
Maeng Han-Joo
Shim Won-Sik
Ahn Sun-Joo
Yu Sang-Soo
Kim Dae-Duk
Shim Chang-Koo
Chung Suk-Jae
|
|
|
Abstract
|
|
|
|
We studied the impact of experimental kidney failure on the pharmacokinetics of a model organic cation and investigated the underlying mechanism(s) of the organic cation transporters. The systemic pharmacokinetics and tissue distribution of triethylmethylammonium (TEMA), a model organic cation, were characterized after intravenous doses of 0.3?30 μmol/kg in rats with or without uranyl nitrate-induced acute renal failure (UN-ARF). To study the effect of endogenous substrates in plasma from UN-ARF rats on organic cation transport, rOCT- or rOCT2-dependent uptake of tetraethylammonium (TEA) was studied in rOCT1-transfected or rOCT2-transfected LLC-PK1 cells, respectively. As a result, the AUC for TEMA was increased, probably because of decreased total clearance, and the tissue-to-plasma concentration ratio (T/P ratio) of TEMA was unchanged in the liver but decreased significantly in the kidneys of UN-ARF rats. In vitro, the uptake of TEA was decreased significantly by adding UN-ARF plasma, compared with control plasma, in rOCT2-overexpressing LLC-PK1 cells, but not in rOCT1-overexpressing LLC-PK1 cells. These observations suggest that the induction of UN-ARF leads to an accumulation of endogenous organic cation(s), probably rOCT2 substrate(s), in the plasma, thereby affecting the TEMA pharmacokinetics and distribution to the kidneys in rats.
|
|
|
KEYWORD
|
|
|
Uranyl nitrate-induced acute renal failure (UN-ARF), Organic cation, Plasma, rOCT2, LLC-PK1
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|