Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human.
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Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I
Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human.
J Pharmacol Exp Ther. 2004 Feb;308(2):438-45. Epub 2003 Nov 10.
- PubMed ID
- 14610227 [ View in PubMed]
- Abstract
The pH-sensitive activity of human organic anion transporting polypeptide OATP-B, which is expressed at the apical membrane of human small intestinal epithelial cells, was functionally characterized. When initial uptake of estrone-3-sulfate, a typical substrate of OATP, was studied kinetically, we observed an increase in V(max) with decrease of pH from 7.4 to 5.0, whereas the change in K(m) was negligible. OATP-B-mediated uptake of estrone-3-sulfate was independent of sodium, chloride, bicarbonate, or glutathione, whereas the proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone exhibited a pH-dependent inhibitory effect, suggesting that a proton gradient is a driving force for OATP-B. When OATP-B was expressed in human embryonic kidney 293 cells, uptake activities for anionic compounds showed various kinds of pH sensitivity. Dehydroepiandrosterone-sulfate, estrone-3-sulfate, and fexofenadine were transported by OATP-B at both neutral and acidic pH, whereas estradiol-17beta-glucuronide, acetic acid, and lactic acid were not transported at all. Transport of taurocholic acid and pravastatin by OATP-B was observed only at acidic pH, demonstrating a pH-sensitive substrate specificity of OATP-B. Because the physiological pH close to the surface of intestinal epithelial cells is acidic, the roles of OATP-B in the small intestine might be different from those in other tissues, such as liver basolateral membrane. Although the driving force for OATP-B has not been fully established, the clarification of factors, such as pH, that affect the OATP-B-activity is essential for an understanding of the physiological and pharmacological relevance of the transporter in the small intestine.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Acetic acid Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateInhibitorDetails Conjugated estrogens Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateDetails Lactic acid Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateInhibitorDetails Pravastatin Solute carrier organic anion transporter family member 2B1 Protein Humans NoSubstrateDetails Taurocholic acid Ileal sodium/bile acid cotransporter Protein Humans UnknownSubstrateInducerDetails Taurocholic acid Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateDetails