Linked Life Data

20797388

Source:http://linkedlifedata.com/resource/pubmed/id/20797388

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-18
pubmed:abstractText
OATP1A2 and OATP2B1 are uptake transporters of the human organic anion transporting polypeptide (OATP) family with a broad substrate spectrum including several endogenous compounds as well as drugs such as the antihistaminic drug fexofenadine and HMG-CoA reductase inhibitors. Both transporters are localized in the apical membrane of human enterocytes. Flavonoids, abundantly occurring in plants, have previously been shown to interact with drug metabolizing enzymes and transporters. However, the impact of flavonoids on OATP1A2 and OATP2B1 transport function has not been analyzed in detail. Therefore, HEK293 cell lines stably expressing OATP1A2 and OATP2B1 were used to investigate the influence of the Ginkgo flavonoids apigenin, kaempferol, and quercetin on the transport activity of OATP1A2 and OATP2B1. K(i) values of all three flavonoids determined from Dixon plot analyses using BSP as substrate indicated a competitive inhibition with quercetin as the most potent inhibitor of OATP1A2 (22.0?M) and OATP2B1 (8.7?M) followed by kaempferol (OATP1A2: 25.2?M, OATP2B1: 15.1?M) and apigenin (OATP1A2: 32.4?M OATP2B1: 20.8?M). Apigenin, kaempferol, and quercetin led to a concentration-dependent decrease of the OATP1A2-mediated fexofenadine transport with IC(50) values of 4.3?M, 12.0?M, and 12.6?M, respectively. The OATP1A2- and OATP2B1-mediated transport of atorvastatin was also efficiently inhibited by apigenin (IC(50) for OATP1A2: 9.3?M, OATP2B1: 13.9?M), kaempferol (IC(50) for OATP1A2: 37.3?M, OATP2B1: 20.7?M) and quercetin (IC(50) for OATP1A2: 13.5?M, OATP2B1: 14.1?M). These data indicate that modification of OATP1A2 and OATP2B1 transport activity by apigenin, kaempferol, and quercetin may be a mechanism for food-drug or drug-drug interactions in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1746-53
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1.
pubmed:affiliation
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nuremberg, Fahrstraße 17, 91054 Erlangen, Germany. Kathrin.mandery@pharmakologie.med.uni-erlangen.de
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't