Transport of somatostatin and substance P by human P‐glycoprotein

Abstract

P-glycoprotein is an efflux pump for a broad spectrum of hydrophobic agents. We found that bioactive peptides including somatostatin and substance P inhibit ATPdependent vincristine binding to P-glycoprotein-overexpressing K562/ADM membrane vesicles. Some of these bioactive peptides including somatostatin stimulate basal ATPase activity of P-glycoprotein; in contrast, other peptides including substance P inhibit it. The K562/ADM membrane vesicles showed an ATPdependent, osmotically sensitive uptake of somatostatin and substance P, which was inhibited by valspodar, an inhibitor of Pglycoprotein. These findings suggested that certain bioactive peptides such as somatostatin and substance P directly interact with human P-glycoprotein as endogenous substrates for Pglycoprotein-mediated transport.

The combination of docetaxel and the somatostatin analogue lanreotide on androgen‐independent docetaxel‐resistant prostate cancer: experimental data

“…There was a 450-fold difference in the expression of the ABC transporter family gene MDR1 in 'highresistance' PC3R cells compared with the PC3wt cells. Uchiyama-Kokubu et al [20] previously investigated whether SST can interact with Pgp; they showed that they interact at a vincristine-binding locus and that SST is transported into plasma membrane vesicles prepared from K562/ADM cells, indicating that Pgp transports SST. Our data suggest that lanreotide could act as a Pgp blocker in 'high-resistance' PC3R cells.…”

Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

“…It was demonstrated that FGF2 was capable of entering the vesicles as evidenced by protection from the protease [37]. A similar method has been used to assess the transmembrane transport behavior of somatostatin [228]. …”