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• W2085705129 abstract "Breast cancer resistance protein (Bcrp/Abcg2) is a new efflux transporter found at the blood-brain barrier (BBB) of humans and pigs. Since it has been hypothesized that Bcrp may act as a new type of efflux transporter at the BBB, we investigated the involvement of Bcrp in the efflux transport of typical substrates, dehydroepiandrosterone sulfate (DHEAS) and mitoxantrone, across the mouse BBB. The expression of Bcrp in mouse brain capillaries was confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemical analysis. The role of Bcrp as an efflux transporter was evaluated using the in situ brain perfusion method in wild-type and P-glycoprotein (P-gp) knockout mice with or without treatment with GF120918 (Elacridar), an inhibitor of both Bcrp and P-gp. The increased brain uptake of [³H]DHEAS and [³H]mitoxantrone by GF120918 in wild-type and P-gp knockout mice suggested the existence of a GF120918-sensitive and P-gp-independent efflux transporter for DHEAS and mitoxantrone across the BBB. However, the brain uptake of [³H]DHEAS in Bcrp knockout mice was comparable with that in wild-type mice, and the effect of GF120918 was still observed in Bcrp knockout mice. In addition, the brain uptake of [³H]mitoxantrone was also similar in wild-type and Bcrp knockout mice. These results suggest that although BCRP is expressed at the BBB it plays a minor role in active efflux transport of DHEAS and mitoxantrone out of brain and that one or more GF120918-sensitive efflux transporters distinct from BCRP or P-gp contributes to the brain efflux of DHEAS and mitoxantrone." @default.
• W2085705129 created "2016-06-24" @default.
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• W2085705129 date "2004-09-24" @default.
• W2085705129 modified "2023-10-16" @default.
• W2085705129 title "Investigation of Efflux Transport of Dehydroepiandrosterone Sulfate and Mitoxantrone at the Mouse Blood-Brain Barrier: A Minor Role of Breast Cancer Resistance Protein" @default.
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• W2085705129 doi "https://doi.org/10.1124/jpet.104.073320" @default.
• W2085705129 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15448171" @default.
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