Abstract
Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent Km values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 μM and 18.5 μM, respectively. The hOat2-mediated uptake of [14C]theophylline and [14C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver.
Footnotes
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.104.003301.
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ABBREVIATIONS: OATP/oatp, organic anion-transporting polypeptide; Oat, organic anion transporter; hOat, human Oat; mOat, mouse Oat; P450, cytochrome P450.
- Received December 13, 2004.
- Accepted February 9, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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