Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pharm Res
2008 Mar 01;253:578-85. doi: 10.1007/s11095-007-9427-9.
Show Gene links
Show Anatomy links
Predominant contribution of rat organic anion transporting polypeptide-2 (Oatp2) to hepatic uptake of beta-lactam antibiotics.
Nakakariya M
,
Shimada T
,
Irokawa M
,
Koibuchi H
,
Iwanaga T
,
Yabuuchi H
,
Maeda T
,
Tamai I
.
???displayArticle.abstract???
PURPOSE: To identify the rat hepatic basolateral transporters involved in the hepatic uptake of beta-lactam antibiotics using nafcillin as a model beta-lactam antibiotic that undergoes extensive biliary excretion.
MATERIALS AND METHODS: Uptake by isolated rat hepatocytes and Xenopus laevis oocytes expressing organic anion transporting peptides (Oatp1, 2, and 4) and organic anion transporter (OAT2) was evaluated.
RESULTS: Nafcillin uptake by isolated rat hepatocytes was saturable with the Km of 210 microM and was significantly inhibited by anionic compounds (estrone-3-sulfate and sulfobromophthalein), but not by cationic compounds (tetraethylammonium and 1-methyl-4-phenylpyridinium). In an in vitro uptake study by Xenopus oocytes expressing hepatic basolateral membrane transporters, nafcillin was transported by multiple Oatps with Km values of 4120 microM (Oatp1/Oatp1a1), 198 microM (Oatp2/Oatp1a4), and 1,570 microM (Oatp4/Oatp1b2), though it was not transported by hOAT2. Comparison of affinity and analysis by the relative activity factor method indicated that Oatp2 is the predominant contributor to the hepatic uptake of nafcillin. Cefadroxil, cefazolin, cefmetazole, cefoperazone, cefsulodin, and cephalexin, though not cefotaxime or ceftriaxone, were also substrates of Oatp2.
CONCLUSION: These findings suggest that Oatp2 plays a key role in the hepatic uptake of nafcillin and most other beta-lactam antibiotics in rats.
Abe,
LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.
2001, Pubmed,
Xenbase
Abe,
LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.
2001,
Pubmed
,
Xenbase
Brogard,
Pharmacokinetics of cephalosporin antibiotics.
1978,
Pubmed
Brogard,
Pharmacokinetics of the new cephalosporins.
1982,
Pubmed
Cantelli Forti,
The influence of lipophilic character on the biliary excretion of penicillins in isolated perfused liver.
1975,
Pubmed
Cattori,
Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver.
2000,
Pubmed
,
Xenbase
Eng,
Effect of nafcillin on hepatic excretory function.
1983,
Pubmed
GLASSMAN,
PHARMACOLOGY AND DISTRIBUTION OF WY-3277 (NAFCILLIN): 6-(2-ETHOXY-1-NAPHTHAMIDO)PENICILLANIC ACID.
1964,
Pubmed
Gründemann,
Drug excretion mediated by a new prototype of polyspecific transporter.
1994,
Pubmed
,
Xenbase
Hirano,
Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans.
2004,
Pubmed
Hsiang,
A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters.
1999,
Pubmed
Ito,
Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport.
2005,
Pubmed
Ito,
Mrp2 is involved in benzylpenicillin-induced choleresis.
2004,
Pubmed
Matsui,
Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys.
1982,
Pubmed
Meier,
Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver.
1997,
Pubmed
Niemi,
High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1).
2004,
Pubmed
Nozawa,
Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms.
2005,
Pubmed
,
Xenbase
Nozawa,
Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity.
2004,
Pubmed
,
Xenbase
Nozawa,
Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin.
2003,
Pubmed
,
Xenbase
Noé,
Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain.
1997,
Pubmed
,
Xenbase
Simonson,
Molecular cloning and characterization of a novel liver-specific transport protein.
1994,
Pubmed
Srinivasan,
Comparative pharmacokinetics of cefoperazone and cefamandole.
1981,
Pubmed
Stowe,
Extrarenal excretion of drugs and chemicals.
1968,
Pubmed
Tamai,
Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.
2000,
Pubmed
Tamai,
Kinetics of benzylpenicillin metabolism in isolated rat hepatocytes.
1987,
Pubmed
Tamai,
Carrier-mediated transport of cefixime, a new cephalosporin antibiotic, via an organic anion transport system in the rat renal brush-border membrane.
1988,
Pubmed
Tamai,
Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C.
2001,
Pubmed
,
Xenbase
Tamai,
Membrane potential-dependent and carrier-mediated transport of cefpiramide, a cephalosporin antibiotic, in canalicular rat liver plasma membrane vesicles.
1990,
Pubmed
Tamai,
Evidence for the existence of a common transport system of beta-lactam antibiotics in isolated rat hepatocytes.
1985,
Pubmed
Terasaki,
Kinetic evidence for a common transport route of benzylpenicillin and probenecid by freshly prepared hepatocytes in rats. Influence of sodium ion, organic anions, amino acids and peptides on benzylpenicillin uptake.
1986,
Pubmed
Tsuda-Tsukimoto,
Characterization of hepatobiliary transport systems of a novel alpha4beta1/alpha4beta7 dual antagonist, TR-14035.
2006,
Pubmed
,
Xenbase
Tsuji,
Uptake of benzylpenicillin, cefpiramide and cefazolin by freshly prepared rat hepatocytes. Evidence for a carrier-mediated transport system.
1986,
Pubmed
Tsuji,
In vivo evidence for carrier-mediated uptake of beta-lactam antibiotics through organic anion transport systems in rat kidney and liver.
1990,
Pubmed
Uchino,
Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1.
2000,
Pubmed
,
Xenbase
Uwai,
Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone.
2002,
Pubmed
,
Xenbase
Wright,
Biliary excretion of cephalosporins in rats: influence of molecular weight.
1980,
Pubmed
Yabuuchi,
Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1.
1998,
Pubmed
,
Xenbase