Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane.

Article Details

Citation

Kobayashi D, Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I

Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane.

J Pharmacol Exp Ther. 2003 Aug;306(2):703-8. Epub 2003 Apr 30.

PubMed ID
12724351 [ View in PubMed
]
Abstract

Some organic anions are absorbed from the gastrointestinal tract through carrier-mediated transport mechanism(s), which may include proton-coupled transport, anion exchange transport, and others. However, the molecular identity of the organic anion transporters localized at the apical membrane of human intestinal epithelial cells has not been clearly demonstrated. In the present study, we focused on human organic anion transporting polypeptide OATP-B and examined its subcellular localization and functionality in the small intestine. Localization of OATP-B was determined by immunohistochemical analysis. Transport properties of estrone-3-sulfate and the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin by OATP-B-transfected human embryonic kidney 293 cells were measured. OATP-B was immunohistochemically localized at the apical membrane of intestinal epithelial cells in humans. Uptake of [3H]estrone-3-sulfate and [14C]pravastatin by OATP-B at pH 5.5 was higher than that at pH 7.4. [3H]Estrone-3-sulfate transport was decreased by pravastatin, aromatic anion compounds, and the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, but not by small anionic compounds, such as lactic acid and acetic acid. The inhibitory effect of pravastatin on the uptake of [3H]estrone-3-sulfate was concentration-dependent, and the IC50 value was 5.5 mM. The results suggested that OATP-B mediates absorption of anionic compounds and its activity may be optimum at the acidic surface microclimate pH of the small intestine. Accordingly, OATP-B plays a role in the absorption of anionic compounds across the apical membrane of human intestinal epithelial cells, although it cannot be decisively concluded that pH-dependent absorption of pravastatin is determined by OATP-B alone.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Acetic acidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Benzoic acidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Inhibitor
Details
Citric acidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Inhibitor
Details
Conjugated estrogensSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Substrate
Details
Lactic acidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
NiacinSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Inhibitor
Details
Oxalic AcidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Inhibitor
Details
Phthalic AcidSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Inhibitor
Details
PravastatinSolute carrier organic anion transporter family member 2B1ProteinHumans
No
Substrate
Details