Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in the intestinal absorption of endothelin receptor antagonist in rats

Pharm Res. 2008 May;25(5):1085-91. doi: 10.1007/s11095-007-9472-4. Epub 2007 Oct 24.


Purpose: 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.

Methods: Uptakes of [(14)C]compound-A by Oatp1a5-expressing Xenopus laevis oocytes and isolated rat enterocytes were evaluated.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Data Interpretation, Statistical
  • Endothelin Receptor Antagonists*
  • Enterocytes / metabolism
  • Female
  • Hydrogen-Ion Concentration
  • Intestinal Absorption / drug effects*
  • Intestinal Absorption / genetics*
  • Kinetics
  • Male
  • Oocytes / metabolism
  • Organic Anion Transporters, Sodium-Independent / genetics*
  • Pyridines / metabolism*
  • Pyridines / pharmacology
  • Rats
  • Sulfobromophthalein
  • Xenopus laevis


  • Endothelin Receptor Antagonists
  • Organic Anion Transporters, Sodium-Independent
  • Pyridines
  • Slco1a5 protein, rat
  • Sulfobromophthalein
  • J 104132