HEPATIC-UPTAKE OF OCTREOTIDE, A LONG-ACTING SOMATOSTATIN ANALOG, VIA A BILE-ACID TRANSPORT-SYSTEM

The hepatic transport mechanism of octreotide (Sandostatin(R)), 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, K-t, and the maximum uptake-rate, J(max), for the uptake of octreotide were 98.1+/-28.4 mu M and 104.6+/-19.7 pmol/mg protein/min, respectively. An energy requirement was demonstrated for [C-14]octreotide uptake since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly reduced the initial uptake rate. [C-14]octreotide uptake was also significantly inhibited by ouabain. [C-14]octreotide uptake was reduced in the absence of Na+ in the uptake medium. [C-14]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, K-i, of 82+/-17 mu M. Moreover, a significant inhibitory effect of octreotide was observed for the Na+ dependent uptake of [C-14]taurocholic acid. These results suggest that octreotide is transported into hepatocytes via a bile acid carrier-mediated system.