azidopine has been researched along with safingol* in 1 studies
1 other study(ies) available for azidopine and safingol
Article | Year |
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Mechanism of inhibition of P-glycoprotein-mediated drug transport by protein kinase C blockers.
P-glycoprotein is a membrane ATPase that transports drugs out of cells and confers resistance to a variety of chemically unrelated drugs (multidrug resistance). P-glycoprotein is phosphorylated by protein kinase C (PKC), and PKC blockers reduce P-glycoprotein phosphorylation and increase drug accumulation. These observations suggest that phosphorylation of P-glycoprotein stimulates drug transport. However, there is evidence that PKC inhibitors directly interact with P-glycoprotein, and therefore the mechanism of their effects on P-glycoprotein-mediated drug transport and the possible role of phosphorylation in the regulation of P-glycoprotein function remain unclear. In the present work, we studied the effects of different kinds of PKC inhibitors on drug transport in cells expressing wild-type human P-glycoprotein and a PKC phosphorylation-defective mutant. We demonstrated that PKC blockers inhibit drug transport hy mechanisms independent of P-glycoprotein phosphorylation. Inhibition by the blockers occurs by (i) direct competition with transported drugs for binding to P-glycoprotein, and (ii) indirect inhibition through a pathway that involves PKC inhibition, but is independent of P-glycoprotein phosphorylation. The effects of the blockers on P-glycoprotein phosphorylation do not seem to play an important role, but the PKC-signaling pathway regulates P-glycoprotein-mediated drug transport. Topics: 3T3 Cells; Affinity Labels; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azides; Biological Transport; Dihydropyridines; Enzyme Inhibitors; Humans; Mice; Phosphorylation; Protein Kinase C; Signal Transduction; Sphingosine; Tumor Cells, Cultured | 1999 |