JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kouzuki, H.
Right arrow Articles by Sugiyama, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kouzuki, H.
Right arrow Articles by Sugiyama, Y.

Vol. 288, Issue 2, 627-634, February 1999

Contribution of Organic Anion Transporting Polypeptide to Uptake of Its Possible Substrates into Rat Hepatocytes1

Hirokazu Kouzuki, Hiroshi Suzuki, Kousei Ito, Rui Ohashi and Yuichi Sugiyama

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Organic anion transporting polypeptide (oatp1) has been cloned from rat liver as one of the transporters responsible for the hepatic uptake of ligands, and its substrate specificity has been determined. However, the contribution of oatp1 to the Na+-independent uptake of ligands into rat hepatocytes remains to be investigated. In the present study, we determined the contribution of oatp1 and examined the uptake of ligands into primary cultured hepatocytes (cultured for 4 h) and into COS-7 cells transiently expressing oatp1 and normalized using estradiol-17beta -D-glucuronide as a reference compound. Western blot analysis indicated that oatp1 was less extensively glycosylated in transfected COS-7 cells, and the expression level in transfectant was one-seventh that in rat liver. The Km values for the uptake of estradiol-17beta -D-glucuronide were similar for cultured hepatocytes and oatp1-transfected COS-7 cells (Km = 12.3 versus 20.4 µM), although the Vmax value for oatp1-transfected COS-7 cells was one-seventh that for cultured hepatocytes (Vmax = 1.30 versus 0.175 nmol/min/mg protein). The contribution of oatp1 to the Na+-independent uptake of taurocholic acid and cholic acid into rat hepatocytes was more than 50 to 60%, whereas the corresponding values for the sulfate-conjugates of estrone and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole were 20 to 30%. In addition, the analysis indicated that the contribution of oatp1 to the Na+-independent uptake of several ligands [glucuronide-conjugate of 6-hydroxy-5,7-dimethyl2-methylamino-4-(3-pyridylmethyl)benzothiazole, ibuprofen, pravastatin, ouabain, and 2,4-dinitrophenyl-S-glutathione] was minimal. Collectively, the transfected COS-7 cells may be used to quantitatively predict oatp1 activity in hepatocytes after correction of its expressed amount. It is also suggested that multiple transport mechanisms are responsible for the Na+-independent uptake of organic anions into hepatocytes.

0022-3565/99/2882-0627$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
N. Ishiguro, K. Maeda, A. Saito, W. Kishimoto, S. Matsushima, T. Ebner, W. Roth, T. Igarashi, and Y. Sugiyama
Establishment of a Set of Double Transfectants Coexpressing Organic Anion Transporting Polypeptide 1B3 and Hepatic Efflux Transporters for the Characterization of the Hepatobiliary Transport of Telmisartan Acylglucuronide
Drug Metab. Dispos., April 1, 2008; 36(4): 796 - 805.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
H. S. Brown, A. Chadwick, and J. B. Houston
Use of Isolated Hepatocyte Preparations for Cytochrome P450 Inhibition Studies: Comparison with Microsomes for Ki Determination
Drug Metab. Dispos., November 1, 2007; 35(11): 2119 - 2126.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
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]

Home page
 Drug Metab. Dispos.Home page
N. Ishiguro, K. Maeda, W. Kishimoto, A. Saito, A. Harada, T. Ebner, W. Roth, T. Igarashi, and Y. Sugiyama
PREDOMINANT CONTRIBUTION OF OATP1B3 TO THE HEPATIC UPTAKE OF TELMISARTAN, AN ANGIOTENSIN II RECEPTOR ANTAGONIST, IN HUMANS
Drug Metab. Dispos., July 1, 2006; 34(7): 1109 - 1115.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
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]

Home page
 Drug Metab. Dispos.Home page
K. A. Hoffmaster, M. J. Zamek-Gliszczynski, G. M. Pollack, and K. L. R. Brouwer
MULTIPLE TRANSPORT SYSTEMS MEDIATE THE HEPATIC UPTAKE AND BILIARY EXCRETION OF THE METABOLICALLY STABLE OPIOID PEPTIDE [D-PENICILLAMINE2,5]ENKEPHALIN
Drug Metab. Dispos., February 1, 2005; 33(2): 287 - 293.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
Y. Shitara, M. Hirano, Y. Adachi, T. Itoh, H. Sato, and Y. Sugiyama
IN VITRO AND IN VIVO CORRELATION OF THE INHIBITORY EFFECT OF CYCLOSPORIN A ON THE TRANSPORTER-MEDIATED HEPATIC UPTAKE OF CERIVASTATIN IN RATS
Drug Metab. Dispos., December 1, 2004; 32(12): 1468 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Shitara, T. Itoh, H. Sato, A. P. Li, and Y. Sugiyama
Inhibition of Transporter-Mediated Hepatic Uptake as a Mechanism for Drug-Drug Interaction between Cerivastatin and Cyclosporin A
J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 610 - 616.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
G. L. Guo, D. R. Johnson, and C. D. Klaassen
Postnatal Expression and Induction by Pregnenolone-16alpha -Carbonitrile of the Organic Anion-Transporting Polypeptide 2 in Rat Liver
Drug Metab. Dispos., March 1, 2002; 30(3): 283 - 288.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
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]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Kouzuki, H. Suzuki, B. Stieger, P. J. Meier, and Y. Sugiyama
Characterization of the Transport Properties of Organic Anion Transporting Polypeptide 1 (oatp1) and Na+/Taurocholate Cotransporting Polypeptide (Ntcp): Comparative Studies on the Inhibitory Effect of their Possible Substrates in Hepatocytes and cDNA-Transfected COS-7 Cells
J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 505 - 511.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Akhteruzzaman, Y. Kato, H. Kouzuki, H. Suzuki, A. Hisaka, B. Stieger, P. J. Meier, and Y. Sugiyama
Carrier-Mediated Hepatic Uptake of Peptidic Endothelin Antagonists in Rats
J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1107 - 1115.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.