![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 287, Issue 1, 37-42, October 1998
Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd.,
Shinagawa-ku, Tokyo 140 (H.I., K.K., H.N., K.N.);
Graduate School of
Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113 (H.K., H.S., Y.S.) and
Division of Clinical Pharmacology and
Toxicology, Department of Medicine, University Hospital, CH-8091
Zurich, Switzerland (B.S., P.J.M.)
The mechanism for hepatic uptake of temocaprilat, an
angiotensin-converting enzyme inhibitor that is predominantly excreted into bile was studied using isolated rat hepatocytes and COS-7 cells
expressing the organic anion transporting polypeptide (oatp1). The
uptake of temocaprilat into isolated rat hepatocytes exhibited saturation with a Km of 20.9 µM and a
Vmax of 0.21 nmol/min/mg protein. This uptake was
temperature sensitive and was significantly reduced by metabolic
inhibitors, a sulfhydryl-modifying reagent and an anion-exchange
inhibitor, although the replacement of Na+ with
Li+ in the medium did not affect the uptake.
[3H]Temocaprilat uptake was inhibited by
estradiol-17
-D-glucuronide and dibromosulphophthalein,
typical substrates for the Na+-independent organic anion
transporter, in a concentration-dependent manner, whereas excess
estradiol-17-D-glucuronide did not completely inhibit
the uptake. Temocaprilat uptake into COS-7 cells transfected with oatp1
cDNA revealed a concentration-dependency with a
Km of 46.7 µM, a value comparable with that
obtained in isolated hepatocytes. The contribution of oatp1 to
carrier-mediated hepatic uptake of temocaprilat was less than 50% by
correcting the uptake clearance with that of
estradiol-17-D-glucuronide. A good linear correlation
was observed for the inhibitory effect of angiotensin-converting enzyme
inhibitors (benazeprilat, cilazaprilat, delaprilat and enalaprilat)
between isolated hepatocytes and oatp1-expressing cells. These data
suggest that oatp1, along with another transporter(s), mediates the
uptake of angiotensin-converting enzyme inhibitors into rat
hepatocytes.
This article has been cited by other articles:
|
|
 |
|
  H. Sun, L. Liu, and K. S. Pang Increased Estrogen Sulfation of Estradiol 17beta-D-Glucuronide in Metastatic Tumor Rat Livers J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 818 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, Y. Cui, A. Y. Chung, Y. Shitara, Y. Sugiyama, D. Keppler, and K. S. Pang Vectorial Transport of Enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in Rat and Human Livers J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 395 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chang, K. S. Pang, P. W. Swaan, and S. Ekins Comparative Pharmacophore Modeling of Organic Anion Transporting Polypeptides: A Meta-Analysis of Rat Oatp1a1 and Human OATP1B1 J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 533 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mizuno, T. Niwa, Y. Yotsumoto, and Y. Sugiyama Impact of Drug Transporter Studies on Drug Discovery and Development Pharmacol. Rev., September 1, 2003; 55(3): 425 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Morita, H. Kusuhara, T. Sekine, H. Endou, and Y. Sugiyama Functional Characterization of Rat Organic Anion Transporter 2 in LLC-PK1 Cells J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1179 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sabordo, B. C. Sallustio, A. M. Evans, and R. L. Nation Hepatic Disposition of the Acyl Glucuronide 1-O-Gemfibrozil-beta -D-glucuronide: Effects of Clofibric Acid, Acetaminophen, and Acetaminophen Glucuronide J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 44 - 50. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. A. M. H. Van Aubel, R. Masereeuw, and F. G. M. Russel Molecular pharmacology of renal organic anion transporters Am J Physiol Renal Physiol, August 1, 2000; 279(2): F216 - F232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Abu-Zahra, A. W. Wolkoff, R. B. Kim, and K. S. Pang Uptake of Enalapril and Expression of Organic Anion Transporting Polypeptide 1 in Zonal, Isolated Rat Hepatocytes Drug Metab. Dispos., July 1, 2000; 28(7): 801 - 806. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ishizuka, K. Konno, T. Shiina, H. Naganuma, K. Nishimura, K. Ito, H. Suzuki, and Y. Sugiyama Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1324 - 1330. [Abstract] [Full Text]
|
|
|
|
 |
|
 U. Eckhardt, A. Schroeder, B. Stieger, M. Hochli, L. Landmann, R. Tynes, P. J. Meier, and B. Hagenbuch Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G1037 - G1042. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
