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This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/G159    most recent 00360.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Mita, S. Articles by Sugiyama, Y. Search for Related Content PubMed PubMed Citation Articles by Mita, S. Articles by Sugiyama, Y.

LIVER AND BILIARY TRACT

Vectorial transport of bile salts across MDCK cells expressing both rat Na⁺-taurocholate cotransporting polypeptide and rat bile salt export pump

¹Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7–3-1 Hongo, Bunkyo-ku, Tokyo, Japan; ²Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zurich, Switzerland; and ³Department of Medicine, University of California, San Diego, California

Submitted 20 August 2003 ; accepted in final form 29 July 2004

Bile salts are predominantly taken up by hepatocytes via the basolateral Na⁺-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and secreted into the bile by the bile salt export pump (BSEP/ABCB11). In the present study, we transfected rat Ntcp and rat Bsep into polarized Madin-Darby canine kidney cells and characterized the transport properties of these cells for eight bile salts. Immunohistochemical staining demonstrated that Ntcp was expressed at the basolateral domains, whereas Bsep was expressed at the apical domains. Basal-to-apical transport of taurocholate across the monolayer expressing only Ntcp and that coexpressing Ntcp/Bsep was observed, whereas the flux across the monolayer of control and Bsep-expressing cells was symmetrical. Basal-to-apical transport of taurocholate across Ntcp/Bsep-coexpressing monolayers was significantly higher than that across monolayers expressing only Ntcp. Kinetic analysis of this vectorial transport of taurocholate gave an apparent K_m value of 13.9 ± 4.7 µM for cells expressing Ntcp alone, which is comparable with 22.2 ± 4.5 µM for cells expressing both Ntcp and Bsep and V_max values of 15.8 ± 4.2 and 60.8 ± 9.0 pmol·min^–1·mg protein^–1 for Ntcp alone and Ntcp and Bsep-coexpressing cells, respectively. Transcellular transport of cholate, glycocholate, taurochenodeoxycholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, ursodeoxycholate, and glycoursodeoxycholate, but not that of lithocholate was also observed across the double transfectant. This double-expressing system can be used as a model to clarify vectorial transport of bile salts across hepatocytes under physiological conditions.

bile salt transporters; hepatocyte; transcellular transport

This article has been cited by other articles:

				S. Mita, H. Suzuki, H. Akita, H. Hayashi, R. Onuki, A. F. Hofmann, and Y. Sugiyama Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G550 - G556. [Abstract] [Full Text] [PDF]