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Interaction of organic anion transporter polypeptides 1B1 and 1B3 with cytostatics (896.7)
Author(s) -
Hagos Yohannes,
Marada Venkata,
Flörl Saskia,
Kühne Annett,
Burckhardt Gerhard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.896.7
Subject(s) - chemistry , vinblastine , paclitaxel , mitoxantrone , transporter , pharmacology , organic anion transporter 1 , abcg2 , biochemistry , atp binding cassette transporter , biology , medicine , cancer , gene , chemotherapy
One of the main functions of liver is the systemic elimination of many exogenous and endogenous substances. In order to perform this function, the initial step is their uptake from blood into the hepatocytes by specific transporter proteins. Many of such proteins constitute the solute carrier (SLC) superfamily. Our work deals with two proteins belonging to the SLC superfamily, the organic anion transporting polypeptides 1B1 and 1B3 which are highly expressed on the basolateral membranes of hepatocytes. We studied these two proteins in stably transfected human embryonic kidney cells using estrone sulfate and cholecystokinin octapeptide 8 (CCK8) as substrates for OATP1B1 and OATP1B3 respectively. Cis‐inhibition experiments were performed to evaluate the interactions of these proteins with cytostatics. Our experiments showed that OATP1B1 interacts strongly with vinblastine and paclitaxel. Ki values of OATP1B1 for vinblastine and paclitaxel were calculated to be 16.87 µM and 0.85 µM respectively. On the other hand, OATP1B3 dependent CCK8 uptake was inhibited in the presence of a variety of cytostatics viz., chlorambucil, bendamustine, doxorubicin, mitoxantrone, vincristine, vinblastine, paclitaxel and etoposide. From our experiments it is clear that these transporters play a crucial role in the uptake of cytostatics into hepatocytes and hence in systemic elimination of these drugs from the body. Grant Funding Source : Deutsche Forschungsgemeinschaft GRK 1034