Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1.

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van Montfoort JE, Stieger B, Meijer DK, Weinmann HJ, Meier PJ, Fattinger KE

Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1.

J Pharmacol Exp Ther. 1999 Jul;290(1):153-7.

PubMed ID

10381771 [ View in PubMed

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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-injected Xenopus laevis oocytes (Km approximately 3.3 mM). In contrast, gadoxetate was not taken up by Oatp2 or OATP cRNA-injected oocytes. Oatp1-mediated gadoxetate uptake (100 microM) could be inhibited by 10 microM bromosulfophthalein (45%), 200 microM taurocholate (92%), 100 microM rifamycin SV (97%), and 100 microM rifampicin (51%). These results show that gadoxetate is a low-affinity substrate of Oatp1. Oatp1-mediated gadoxetate transport demonstrated a similar apparent Km value and cis-inhibition pattern as previously determined in rats in vivo, indicating that Oatp1 is significantly involved in gadoxetate uptake into rat liver.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Rifampicin	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Inhibitor	Details
Taurocholic acid	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate Inhibitor Inducer	Details