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Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide.
Drug Des Devel Ther. 2015; 9:643-53.DD

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. OATP1B1- and 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.

Authors+Show Affiliations

College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea.Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea.Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea.Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea.College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25653502

Citation

Jeong, Hyeon-Uk, et al. "Organic Anion Transporter 3- and Organic Anion Transporting Polypeptides 1B1- and 1B3-mediated Transport of Catalposide." Drug Design, Development and Therapy, vol. 9, 2015, pp. 643-53.
Jeong HU, Kwon M, Lee Y, et al. Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide. Drug Des Devel Ther. 2015;9:643-53.
Jeong, H. U., Kwon, M., Lee, Y., Yoo, J. S., Shin, D. H., Song, I. S., & Lee, H. S. (2015). Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide. Drug Design, Development and Therapy, 9, 643-53. https://doi.org/10.2147/DDDT.S75400
Jeong HU, et al. Organic Anion Transporter 3- and Organic Anion Transporting Polypeptides 1B1- and 1B3-mediated Transport of Catalposide. Drug Des Devel Ther. 2015;9:643-53. PubMed PMID: 25653502.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2015/01/22/ PY - 2015/2/6/entrez PY - 2015/2/6/pubmed PY - 2015/9/10/medline KW - OAT3 KW - OATP1B1 KW - OATP1B3 KW - catalposide KW - drug transporters KW - herb–drug interaction SP - 643 EP - 53 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 9 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 (K m) =41.5 μM, maximum uptake rate (V max) =46.2 pmol/minute, and intrinsic clearance (CL int) =1.11 μL/minute. OATP1B1- and 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. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/25653502/Organic_anion_transporter_3__and_organic_anion_transporting_polypeptides_1B1__and_1B3_mediated_transport_of_catalposide_ L2 - https://dx.doi.org/10.2147/DDDT.S75400 DB - PRIME DP - Unbound Medicine ER -