Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin.
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Nozawa T, Tamai I, Sai Y, Nezu J, Tsuji A
Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin.
J Pharm Pharmacol. 2003 Jul;55(7):1013-20.
- PubMed ID
- 12906759 [ View in PubMed]
- 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-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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Conjugated estrogens Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorDetails DADLE Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownNot Available Details Levocarnitine Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownInhibitorDetails Quinidine Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownInhibitorDetails Taurocholic acid Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorInducerDetails