title: Hepatic uptake of octreotide, a long-acting somatostatin analogue, via a bile acid transport system.
abstract: The hepatic transport mechanism of octreotide (Sandostatin), a somatostatin analogue, was studied using freshly prepared rat hepatocytes. The initial uptake rate of octreotide represented exclusively a saturable transport process. The half-saturation constant, Kt, and the maximum uptake-rate, Jmax, for the uptake of octreotide were 91.1 +/- 28.4 microM and 104.6 +/- 19.7 pmol/mg protein/min, respectively. An energy requirement was demonstrated for [14C]octreotide uptake since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly reduced the initial uptake rate. [14C]octreotide uptake was also significantly inhibited by ouabain. [14C]octreotide uptake was reduced in the absence of Na+ in the uptake medium. [14C]octreotide uptake was significantly inhibited by bile acids, iodipamide, d-tubocurarine, whereas it was not inhibited by bilirubin, TEMA and insulin. Competitive inhibition of taurocholic acid was observed for octreotide uptake with the inhibition constant, Ki, of 82 +/- 17 microM. Moreover, a significant inhibitory effect of octreotide was observed for the Na+ dependent uptake of [14C]taurocholic acid. These results suggest that octreotide is transported into hepatocytes via a bile acid carrier-mediated system.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Terasaki
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: C
authors.initials: C
authors.lastname: Itoho
authors.forename: I
authors.initials: I
authors.lastname: Tamai
authors.forename: M
authors.initials: M
authors.lastname: Lemaire
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001667:Binding, Competitive; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D015282:Octreotide / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D013656:Taurocholic Acid; D012964:Sodium; D015282:Octreotide