inostamycin and azidopine

The mechanism of inostamycin action was further studied. When multidrug-resistant KB-C4 cells were preincubated with inostamycin for 30 min, the accumulation of [3H]vinblastine was increased for as long as 48 h thereafter. Inostamycin inhibited azidopine binding to P-glycoprotein, even after KB plasma membranes had been preincubated with inostamycin and washed. Carbon 14-labeled inostamycin bound to KB plasma membranes irreversibly, but the binding capacity did not parallel the amount of P-glycoprotein in three KB cell lines. Inostamycin was found to interact specifically with purified phosphatidylethanolamine. These results suggest that inostamycin can inhibit P-glycoprotein irreversibly by binding to plasma membranes irreversibly through phosphatidylethanolamine.

Topics: Anti-Bacterial Agents; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azides; Binding, Competitive; Cell Membrane; Dihydropyridines; Furans; Humans; KB Cells; Phosphatidylethanolamines; Sensitivity and Specificity; Tritium; Vinblastine