Abstract
Gadoxetate is a new hepatobiliary magnetic resonance imaging contrast agent. It is specifically taken up by hepatocytes, and its uptake can be inhibited by the coadministration of bromosulfophthalein, suggesting an involvement of one or several of the cloned organic anion transporting polypeptides Oatp1, Oatp2, and/or OATP. In this study, we demonstrated saturable uptake of gadoxetate by Oatp1 cRNA-injectedXenopus laevis oocytes (Km ∼ 3.3 mM). In contrast, gadoxetate was not taken up by Oatp2 or OATP cRNA-injected oocytes. Oatp1-mediated gadoxetate uptake (100 μM) could be inhibited by 10 μM bromosulfophthalein (45%), 200 μM taurocholate (92%), 100 μM rifamycin SV (97%), and 100 μM rifampicin (51%). These results show that gadoxetate is a low-affinity substrate of Oatp1. Oatp1-mediated gadoxetate transport demonstrated a similar apparentKm value and cis-inhibition pattern as previously determined in rats in vivo, indicating that Oatp1 is significantly involved in gadoxetate uptake into rat liver.
Footnotes
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Send reprint requests to: Dr. K. Fattinger, Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091 Zürich/Switzerland. E-mail:fattinge{at}kpt.unizh.ch
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↵1 This work was supported by the Swiss National Science Foundation Grants 3100-045536.95 and 3200-052190.97. J. van M. was supported by an Ubbo Emmius scholarship from the University of Groningen. K.F. was supported by a SCORE Career Development Award from the Swiss National Science Foundation. A preliminary report of this study was presented at the 49th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Chicago, November 6 through 10, 1998, and published in abstract form [Hepatology (1998) 28:180A).
- Abbreviations:
- BSP
- bromosulfophthalein
- Oatp
- organic anion transporting polypeptide
- Received January 12, 1999.
- Accepted March 11, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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