Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules

Shin ichi Akanuma; Rintaro Kida; Ai Tsuchiyama; Masanori Tachikawa; Yoshiyuki Kubo; Ken ichi Hosoya

doi:10.1016/j.dmpk.2019.04.001

Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules

Shin ichi Akanuma, Rintaro Kida, Ai Tsuchiyama, Masanori Tachikawa, Yoshiyuki Kubo, Ken ichi Hosoya

PHA - Life and Pharmaceutical Science

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

6 Citations (Scopus)

Abstract

It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.

Original language	English
Pages (from-to)	239-246
Number of pages	8
Journal	Drug metabolism and pharmacokinetics
Volume	34
Issue number	4
DOIs	https://doi.org/10.1016/j.dmpk.2019.04.001
Publication status	Published - 2019 Aug

Keywords

Clearance
Hepatocyte
Heterogeneity
Liver
Oatp1a4
Organic anion-transporting polypeptide
Sulforhodamine-101
Zonation

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Pharmacology (medical)

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10.1016/j.dmpk.2019.04.001

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@article{c198b6efd30145018361a32d1661f564,

title = "Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules",

abstract = "It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.",

keywords = "Clearance, Hepatocyte, Heterogeneity, Liver, Oatp1a4, Organic anion-transporting polypeptide, Sulforhodamine-101, Zonation",

author = "Akanuma, {Shin ichi} and Rintaro Kida and Ai Tsuchiyama and Masanori Tachikawa and Yoshiyuki Kubo and Hosoya, {Ken ichi}",

note = "Funding Information: The authors thank Dr. Takaaki Abe (Tohoku University, Japan) and Dr. Yuma Tega (Teikyo University, Japan) for supplying the pGEM-HE vector and advising the transport studies using isolated rat hepatocytes and transporter-expressing X. laevis oocytes, respectively. This study was financially supported by Japan Society for the Promotion of Science KAKENHI [Grant Numbers JP16H05110 and JP16K08365] and Core-to-Core Program (B. Asia-Africa Science Platforms). Funding Information: The authors thank Dr. Takaaki Abe (Tohoku University, Japan) and Dr. Yuma Tega (Teikyo University, Japan) for supplying the pGEM-HE vector and advising the transport studies using isolated rat hepatocytes and transporter-expressing X. laevis oocytes, respectively. This study was financially supported by Japan Society for the Promotion of Science KAKENHI [Grant Numbers JP16H05110 and JP16K08365 ] and Core-to-Core Program (B. Asia-Africa Science Platforms). Publisher Copyright: {\textcopyright} 2019 The Japanese Society for the Study of Xenobiotics",

year = "2019",

month = aug,

doi = "10.1016/j.dmpk.2019.04.001",

language = "English",

volume = "34",

pages = "239--246",

journal = "Drug Metabolism and Pharmacokinetics",

issn = "1347-4367",

publisher = "Japanese Society for the Study of Xenobiotics",

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T1 - Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules

AU - Akanuma, Shin ichi

AU - Kida, Rintaro

AU - Tsuchiyama, Ai

AU - Tachikawa, Masanori

AU - Kubo, Yoshiyuki

AU - Hosoya, Ken ichi

N1 - Funding Information: The authors thank Dr. Takaaki Abe (Tohoku University, Japan) and Dr. Yuma Tega (Teikyo University, Japan) for supplying the pGEM-HE vector and advising the transport studies using isolated rat hepatocytes and transporter-expressing X. laevis oocytes, respectively. This study was financially supported by Japan Society for the Promotion of Science KAKENHI [Grant Numbers JP16H05110 and JP16K08365] and Core-to-Core Program (B. Asia-Africa Science Platforms). Funding Information: The authors thank Dr. Takaaki Abe (Tohoku University, Japan) and Dr. Yuma Tega (Teikyo University, Japan) for supplying the pGEM-HE vector and advising the transport studies using isolated rat hepatocytes and transporter-expressing X. laevis oocytes, respectively. This study was financially supported by Japan Society for the Promotion of Science KAKENHI [Grant Numbers JP16H05110 and JP16K08365 ] and Core-to-Core Program (B. Asia-Africa Science Platforms). Publisher Copyright: © 2019 The Japanese Society for the Study of Xenobiotics

PY - 2019/8

Y1 - 2019/8

N2 - It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.

AB - It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.

KW - Clearance

KW - Hepatocyte

KW - Heterogeneity

KW - Liver

KW - Oatp1a4

KW - Organic anion-transporting polypeptide

KW - Sulforhodamine-101

KW - Zonation

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U2 - 10.1016/j.dmpk.2019.04.001

DO - 10.1016/j.dmpk.2019.04.001

M3 - Article

AN - SCOPUS:85065072483

SN - 1347-4367

VL - 34

SP - 239

EP - 246

JO - Drug Metabolism and Pharmacokinetics

JF - Drug Metabolism and Pharmacokinetics

IS - 4

ER -

Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules

Abstract

Keywords

ASJC Scopus subject areas

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