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Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin.
Nozawa, Takashi; Tamai, Ikumi; Sai, Yoshimichi; Nezu, Jun-Ichi; Tsuji, Akira.
Afiliación
  • Nozawa T; Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
J Pharm Pharmacol ; 55(7): 1013-20, 2003 Jul.
Article en En | MEDLINE | ID: mdl-12906759
The objective of this study was to examine the transport activity of the human organic anion transporter OATP-C (SLC21A6) for oligopeptides that are eliminated rapidly from the systemic circulation. We focused on an opioid peptide analogue, [D-Ala(2), D-Leu(5)]-enkephalin (DADLE), a linear pentapeptide modified to be stable. [(3)H]DADLE was taken up by rat isolated hepatocytes in a saturable manner and highly accumulated in the liver after intravenous administration to rats. The uptake of [(3)H]DADLE by the isolated hepatocytes was inhibited by several organic anions and pentapeptides, but not by tetra- or tripeptides. When OATP-C was expressed in Xenopus laevis oocytes, a significant increase in uptake of [(3)H]DADLE was observed. Moreover, the inhibitory effects of various compounds, including some peptides, on [(3)H]estrone-3-sulfate uptake by OATP-C were similar to those observed in [(3)H]DADLE uptake by rat isolated hepatocytes. In conclusion, it was demonstrated that OATP-C contributes to the rapid hepatic excretion of peptides and peptide-mimetic drugs.
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Base de datos: MEDLINE Asunto principal: Leucina Encefalina-2-Alanina / Hepatocitos / Transportador 1 de Anión Orgánico Específico del Hígado / Estrona Límite: Animals Idioma: En Revista: J Pharm Pharmacol Año: 2003 Tipo del documento: Article País de afiliación: Japón
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Base de datos: MEDLINE Asunto principal: Leucina Encefalina-2-Alanina / Hepatocitos / Transportador 1 de Anión Orgánico Específico del Hígado / Estrona Límite: Animals Idioma: En Revista: J Pharm Pharmacol Año: 2003 Tipo del documento: Article País de afiliación: Japón