Directional Drug Transport through Membrane-Supported Monolayers of Human Liver-Derived Cell Lines

The aim of this work is to develop a new assay system for screening biliary excretion drugs. When monolayers of human liver-derived cell lines HepG2 and Huh-7 were grown on an insert membrane, the efflux ratio (ER: ratio of the apparent permeability coefficient in the basal-to-apical direction (Papp...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2022/01/01, Vol.45(1), pp.150-153
Main Authors: Mizoi, Kenta, Kobayashi, Misako, Mashimo, Arisa, Matsumoto, Eiko, Masuda, Norio, Itoh, Manabu, Ueno, Toshiya, Tachiki, Hidehisa, Ishida, Seiichi, Ogihara, Takuo
Format: Article
Language:English
Subjects:
Breast cancer
direction
Drug screening
Excretion
Gene expression
Hepatocytes
HepG2
Huh-7
Liver
membrane
Membrane permeability
mRNA
Multidrug resistance
Multidrug resistant organisms
P-Glycoprotein
transport
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Summary:The aim of this work is to develop a new assay system for screening biliary excretion drugs. When monolayers of human liver-derived cell lines HepG2 and Huh-7 were grown on an insert membrane, the efflux ratio (ER: ratio of the apparent permeability coefficient in the basal-to-apical direction (Papp,B-to-A) to that in the apical to basal direction (Papp,A-to-B)) of sulfobromophthalein (BSP), a model substrate of multidrug resistance-associated protein 2 (MRP2), was greater than 1.0, indicating transport of BSP in the efflux direction. The efflux transport was significantly suppressed by MK-571, an inhibitor of MRPs, in both cell lines. Expression of MRP2 mRNA in HepG2 and Huh-7 was 3.5- and 1.4-fold higher, respectively, than in primary human hepatocytes, while expression of P-glycoprotein and breast cancer resistance protein mRNAs was markedly lower, supporting the idea that MRP2 is the main mediator of directional BSP transport in this assay system. The advantage of our system is the potential to quantitatively evaluate biliary excretion of MRP2 substrates in vitro.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b21-00583