Presence of an H+/Quinidine Antiport System in Madin–Darby Canine Kidney Cells

Fukao, Miki; Kondo, Eri; Hattori, Ryutaro; Horie, Asuka; Hashimoto, Yoshiaki

doi:10.1007/s13318-015-0314-1

Cited by 6 publications

(1 citation statement)

References 11 publications

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“…It has been reported that the efflux ratio of quinidine is comparable to that of rhodamine 123 in human P-gp-overexpressing MDCK cells and Caco-2 cells . It is unclear why there is a discrepancy in the directional transport of rhodamine 123 and quinidine in hiPS-BMECs, but possible explanations include (1) some other transporter, which shows similar responses to inhibitors to P-gp, mediates directional transport of rhodamine 123, or (2) since quinidine is known to be a substrate of not only P-gp but also H + /OC antiporter, an active influx transporter, transport mediated by another system, possibly H + /OC antiporter, may mask the role of P-gp in quinidine transport in hiPS-BMECs. Further studies will be needed to resolve this.…”

Section: Discussionmentioning

confidence: 99%

Expression and Functional Characterization of Drug Transporters in Brain Microvascular Endothelial Cells Derived from Human Induced Pluripotent Stem Cells

Kurosawa¹,

Tega²,

Higuchi³

et al. 2018

Mol. Pharmaceutics

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Brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPS-BMECs) have been proposed as a new blood–brain barrier model, but their transport function has not been fully clarified. Therefore, in this study, we investigated the gene expression and function of transporters in hiPS-BMECs by means of quantitative reverse transcription-PCR, in vitro transcellular transport studies, and uptake experiments. mRNAs encoding ABC and SLC transporters, such as BCRP, MCT1, CAT1, and GLAST, were highly expressed in hiPS-BMECs. Transcellular transport studies showed that prazosin, [14C]l-lactate, [3H]l-arginine, and [3H]l-glutamate (substrates of BCRP, MCT1, CAT1, and GLAST, respectively) were transported asymmetrically across the hiPS-BMEC monolayer. Substrates of LAT1, OCTN2, CAT1, GLAST, MCT1, and proton-coupled organic cation (H+/OC) antiporter were taken up by hiPS-BMECs in a time-, temperature-, and concentration-dependent manner, and the uptakes were markedly decreased by inhibitors of the corresponding transporter. These results indicate that hiPS-BMECs express multiple nutrient and drug transporters.

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Section: Discussionmentioning

confidence: 99%