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 May 01;255:1085-91. doi: 10.1007/s11095-007-9472-4.
Show Gene links
Show Anatomy links
Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in the intestinal absorption of endothelin receptor antagonist in rats.
Tani T
,
Gram LK
,
Arakawa H
,
Kikuchi A
,
Chiba M
,
Ishii Y
,
Steffansen B
,
Tamai I
.
Abstract
To assess the contribution of organic anion transporting polypeptide 1a5 (Oatp1a5/Oatp3) in the intestinal absorption of an orally active endothelin receptor antagonist, (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylene-dioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic acid (compound-A) in rats. Uptakes of [(14)C]compound-A by Oatp1a5-expressing Xenopus laevis oocytes and isolated rat enterocytes were evaluated. The uptake of compound-A by Oatp1a5-expressing oocytes was significantly higher than that by water-injected oocytes and Oatp1a5-mediated uptake was saturable with K(m) value of 116 microM. Compound-A was taken up into isolated enterocytes in time- and concentration-dependent manners and the estimated K(m) value was 83 microM, which was close to that for the Oatpt1a5-mediated uptake in oocytes. Both uptakes of compound-A by Oatp1a5-expressing oocytes and enterocytes were pH-sensitive with significantly higher uptake at acidic pH than those at neutral pH. Uptakes of compound-A into Oatp1a5-expressing oocytes and enterocytes were significantly decreased in the presence of Oatp1a5 substrates such as bromosulfophthalein and taurocholic acid. These results consistently suggested that Oatp1a5 is contributing to the intestinal absorption of compound-A at least in part, and the transporter-mediated absorption seems to be maximized at the acidic microenvironment of epithelial cells in the small intestine in rats.
Cattori,
Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3.
2001, Pubmed,
Xenbase
Cattori,
Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3.
2001,
Pubmed
,
Xenbase
Dresser,
Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.
2002,
Pubmed
Glaeser,
Intestinal drug transporter expression and the impact of grapefruit juice in humans.
2007,
Pubmed
Hagenbuch,
Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties.
2004,
Pubmed
Katsura,
Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation.
2003,
Pubmed
Kikuchi,
Transporter-mediated intestinal absorption of fexofenadine in rats.
2006,
Pubmed
,
Xenbase
Kimmich,
Preparation and properties of mucosl epithelial cells isolated frmsmall intestine of the chicken.
1970,
Pubmed
Kobayashi,
Hepatobiliary transport of a nonpeptidic endothelin antagonist, (+)-(5S,6R,7R)-2-butyl-7-[2((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl) cyclopentenol[1,2-b]pyridine-6-carboxylic acid: uptake by isolated rat hepatocytes and canalicular membrane vesicles.
2003,
Pubmed
Kobayashi,
Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane.
2003,
Pubmed
Lucas,
Determination of acid surface pH in vivo in rat proximal jejunum.
1983,
Pubmed
Maeda,
Identification of influx transporter for the quinolone antibacterial agent levofloxacin.
2007,
Pubmed
,
Xenbase
Nishikibe,
Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist.
1999,
Pubmed
Nishio,
Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate.
2000,
Pubmed
,
Xenbase
Nozawa,
Role of anion exchange transporter PAT1 (SLC26A6) in intestinal absorption of organic anions.
2004,
Pubmed
Nozawa,
Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human.
2004,
Pubmed
Tamai,
Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.
2000,
Pubmed
Tamai,
Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1.
1999,
Pubmed
Tamai,
The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine.
1997,
Pubmed
,
Xenbase
Thwaites,
H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine.
2007,
Pubmed
Tsuji,
Carrier-mediated intestinal transport of drugs.
1996,
Pubmed
Walters,
Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.
2000,
Pubmed
Yamaoka,
A pharmacokinetic analysis program (multi) for microcomputer.
1981,
Pubmed