Linked Life Data

14610227

Source:http://linkedlifedata.com/resource/pubmed/id/14610227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-28
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
308
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
438-45
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human.
pubmed:affiliation
Department of Molecular Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't