Organic anion transporter 3- and organic anion transporting polypeptides 1B1-and 1B3-mediated transport of catalposide

Hyeon Uk Jeong; Mihwa Kwon; Yongnam Lee; Ji Seok Yoo; Dae Hee Shin; Im Sook Song; Hye Suk Lee

doi:10.2147/DDDT.S75400

Organic anion transporter 3- and organic anion transporting polypeptides 1B1-and 1B3-mediated transport of catalposide

Hyeon Uk Jeong
, Mihwa Kwon
, Yongnam Lee
, Ji Seok Yoo
, Dae Hee Shin
, Im Sook Song
, Hye Suk Lee

The Catholic University of Korea
Kyungpook National University
Yungjin Pharm. Co., Ltd.

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

18 Scopus citations

Abstract

We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1), OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic cation transporter 1 (OCT1), OCT2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3) and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3). The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (K_m) =41.5 μM, maximum uptake rate (V_max) =46.2 pmol/minute, and intrinsic clearance (CL_int) =1.11 μL/minute. OATP1B1and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CL_int values of 0.035 and 0.034 μL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µM, respectively. However, catalposide did not significantly inhibit the transport activities of OCT1, OCT2, OAT1, P-gp, or BCRP. In conclusion, OAT3, OATP1B1, and OATP1B3 are major transporters that may regulate the pharmacokinetic properties and may cause herb–drug interactions of catalposide, although their clinical relevance awaits further evaluation.

Original language	English
Pages (from-to)	643-653
Number of pages	11
Journal	Drug Design, Development and Therapy
Volume	9
DOIs	https://doi.org/10.2147/DDDT.S75400
State	Published - 22 Jan 2015

Bibliographical note

Publisher Copyright:
© 2015 Jeong et al. This work is published by Dove Medical Press Limited.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Catalposide
Drug transporters
Herb–drug interaction
OAT3
OATP1B1
OATP1B3

Access to Document

10.2147/DDDT.S75400

Cite this

@article{ccf40c07a61f49328d87e3adfebf8509,

title = "Organic anion transporter 3- and organic anion transporting polypeptides 1B1-and 1B3-mediated transport of catalposide",

abstract = "We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1), OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic cation transporter 1 (OCT1), OCT2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3) and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3). The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km) =41.5 μM, maximum uptake rate (Vmax) =46.2 pmol/minute, and intrinsic clearance (CLint) =1.11 μL/minute. OATP1B1and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 μL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µM, respectively. However, catalposide did not significantly inhibit the transport activities of OCT1, OCT2, OAT1, P-gp, or BCRP. In conclusion, OAT3, OATP1B1, and OATP1B3 are major transporters that may regulate the pharmacokinetic properties and may cause herb{\textendash}drug interactions of catalposide, although their clinical relevance awaits further evaluation.",

keywords = "Catalposide, Drug transporters, Herb{\textendash}drug interaction, OAT3, OATP1B1, OATP1B3",

author = "Jeong, \{Hyeon Uk\} and Mihwa Kwon and Yongnam Lee and Yoo, \{Ji Seok\} and Shin, \{Dae Hee\} and Song, \{Im Sook\} and Lee, \{Hye Suk\}",

note = "Publisher Copyright: {\textcopyright} 2015 Jeong et al. This work is published by Dove Medical Press Limited.",

year = "2015",

month = jan,

day = "22",

doi = "10.2147/DDDT.S75400",

language = "English",

volume = "9",

pages = "643--653",

journal = "Drug Design, Development and Therapy",

issn = "1177-8881",

publisher = "Dove Medical Press Ltd",

}

TY - JOUR

T1 - Organic anion transporter 3- and organic anion transporting polypeptides 1B1-and 1B3-mediated transport of catalposide

AU - Jeong, Hyeon Uk

AU - Kwon, Mihwa

AU - Lee, Yongnam

AU - Yoo, Ji Seok

AU - Shin, Dae Hee

AU - Song, Im Sook

AU - Lee, Hye Suk

PY - 2015/1/22

Y1 - 2015/1/22

N2 - We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1), OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic cation transporter 1 (OCT1), OCT2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3) and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3). The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km) =41.5 μM, maximum uptake rate (Vmax) =46.2 pmol/minute, and intrinsic clearance (CLint) =1.11 μL/minute. OATP1B1and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 μL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µM, respectively. However, catalposide did not significantly inhibit the transport activities of OCT1, OCT2, OAT1, P-gp, or BCRP. In conclusion, OAT3, OATP1B1, and OATP1B3 are major transporters that may regulate the pharmacokinetic properties and may cause herb–drug interactions of catalposide, although their clinical relevance awaits further evaluation.

AB - We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1), OAT3, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic cation transporter 1 (OCT1), OCT2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3) and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3). The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km) =41.5 μM, maximum uptake rate (Vmax) =46.2 pmol/minute, and intrinsic clearance (CLint) =1.11 μL/minute. OATP1B1and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 μL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µM, respectively. However, catalposide did not significantly inhibit the transport activities of OCT1, OCT2, OAT1, P-gp, or BCRP. In conclusion, OAT3, OATP1B1, and OATP1B3 are major transporters that may regulate the pharmacokinetic properties and may cause herb–drug interactions of catalposide, although their clinical relevance awaits further evaluation.

KW - Catalposide

KW - Drug transporters

KW - Herb–drug interaction

KW - OAT3

KW - OATP1B1

KW - OATP1B3

UR - https://www.scopus.com/pages/publications/84921836701

U2 - 10.2147/DDDT.S75400

DO - 10.2147/DDDT.S75400

M3 - Article

C2 - 25653502

AN - SCOPUS:84921836701

SN - 1177-8881

VL - 9

SP - 643

EP - 653

JO - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

ER -

Organic anion transporter 3- and organic anion transporting polypeptides 1B1-and 1B3-mediated transport of catalposide

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this