Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats

Ryutaro Matsui; Ryutaro Hattori; Youhei Usami; Masumi Koyama; Yuki Hirayama; Emi Matsuba; Yukiya Hashimoto

doi:10.1016/j.dmpk.2017.11.313

Functional characteristics of a renal H⁺/lipophilic cation antiport system in porcine LLC-PK₁ cells and rats

Ryutaro Matsui, Ryutaro Hattori, Youhei Usami, Masumi Koyama, Yuki Hirayama, Emi Matsuba, Yukiya Hashimoto^*

^*Corresponding author for this work

Clinical Pharmacokinetics

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

We have recently found an H⁺/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H⁺/lipophilic cation antiport system is expressed in porcine LLC-PK₁ cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK₁ cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK₁ cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK₁ cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK₁ cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H⁺/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK₁ cells. Moreover, the H⁺/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.

Original language	English
Pages (from-to)	96-102
Number of pages	7
Journal	Drug Metabolism and Pharmacokinetics
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.dmpk.2017.11.313
State	Published - 2018/02

Keywords

Bisoprolol
H/lipophilic cation antiport system
LLC-PK cells
Quinidine
Rat
Renal excretion

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Pharmacology (medical)

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10.1016/j.dmpk.2017.11.313

Cite this

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title = "Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats",

abstract = "We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H+/lipophilic cation antiport system is expressed in porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H+/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.",

keywords = "Bisoprolol, H/lipophilic cation antiport system, LLC-PK cells, Quinidine, Rat, Renal excretion",

author = "Ryutaro Matsui and Ryutaro Hattori and Youhei Usami and Masumi Koyama and Yuki Hirayama and Emi Matsuba and Yukiya Hashimoto",

note = "Publisher Copyright: {\textcopyright} 2017 The Japanese Society for the Study of Xenobiotics",

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AU - Matsui, Ryutaro

AU - Hattori, Ryutaro

AU - Usami, Youhei

AU - Koyama, Masumi

AU - Hirayama, Yuki

AU - Matsuba, Emi

AU - Hashimoto, Yukiya

PY - 2018/2

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N2 - We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H+/lipophilic cation antiport system is expressed in porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H+/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.

AB - We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H+/lipophilic cation antiport system is expressed in porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H+/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.

KW - Bisoprolol

KW - H/lipophilic cation antiport system

KW - LLC-PK cells

KW - Quinidine

KW - Rat

KW - Renal excretion

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