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- Title
Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala<sup>2</sup>, D-Leu<sup>5</sup>]-enkephalin.
- Authors
Takashi Nozawa; Ikumi Tamai; Yoshimichi Sai; Jun-Ichi Nezu; Akira Tsuji
- Abstract
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-Ala2, D-Leu5]-enkephalin (DADLE), a linear pentapeptide modified to be stable. [3H]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 [3H]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 [3H]DADLE was observed. Moreover, the inhibitory effects of various compounds, including some peptides, on [3H]estrone-3-sulfate uptake by OATP-C were similar to those observed in [3H]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.
- Subjects
LIVER cells; PROTEINS; PEPTIDES; ESTROGEN
- Publication
Journal of Pharmacy & Pharmacology, 2003, Vol 55, Issue 7, p1013
- ISSN
0022-3573
- Publication type
Article