We have investigated the involvement of intracellular pH (pH(i)) in the regulation of P-glycoprotein (P-gp) in K562/DOX cells. The selective Na(+)/H(+) exchanger1 (NHE1) inhibitor cariporide and the "high K(+)" buffer were used to induce the sustained intracellular acidification of the K562/DOX cells that exhibited more alkaline pH(i) than the K562 cells. The acidification resulted in the decre...

More than 30 000 patients have been enrolled in trials assessing the efficacy of glycoprotein (GP) IIb/IIIa inhibitors in unstable angina (UA) or non– ST-segment elevation MI (NSTEMI). The initial trials demonstrated that the use of a GP IIb/IIIa inhibitor resulted in a significant decrease in the rate of death or nonfatal myocardial infarction.1,2 More recently, however, the GP IIb/IIIa inhibi...

The (-)- and (+)-clausenamide (CLA) enantiomers have different pharmacokinetic effects in animals, but their association with putative stereoselective regulation of P-glycoprotein (P-gp) remains unclear. Using three cells expressing P-gp-Caco-2, KBv and rat brain microvessel endothelial cells(RBMEC), this study investigated the association of CLA enantiomers with P-gp. The results showed that t...

The effect of benznidazole (BZL) on the expression and activity of P-glycoprotein (P-gp, ABCB1) and multidrug resistance-associated protein 2 (MRP2, ABCC2), the two major transporters of endogenous and exogenous compounds, was evaluated in differentiated THP-1 cells. BZL induced P-gp and MRP2 proteins in a concentration-dependent manner. The increase in mRNA levels of both transporters suggests...

P-Glycoprotein (P-gp, ABCB1) plays a significant role in determining the ADMET properties of drugs and drug candidates. Substrates of P-gp are not only subject to multidrug resistance (MDR) in tumor therapy, they are also associated with poor pharmacokinetic profiles. In contrast, inhibitors of P-gp have been advocated as modulators of MDR. However, due to the polyspecificity of P-gp, knowledge...

Pharmacological inhibition of liver GP (glycogen phosphorylase), which is currently being studied as a treatment for Type II (non-insulin-dependent) diabetes, may affect muscle glycogen metabolism. In the present study, we analysed the effects of the GP inhibitor CP-91149 on non-engineered or GP-overexpressing cultured human muscle cells. We found that CP-91149 treatment decreased muscle GP act...

This paper examines determinants of creditor recoveries from defaulted debt instruments. First, we argue that to properly measure a debt instrument’s relative position in a firm’s debt structure, debt pari passu to the instrument must be accounted for. We thus propose a new measure of seniority and find that it is the most important determinant of recovery rates. Second, firm-level variables, e...

etoposide, a widely used anticancer drug, exhibits low and variable oral bioavailability mainly because of being substrate for the efflux transporter, p-glycoprotein (p-gp). therefore, the present study was aimed to investigate the effect of d-α-tocopherol polyethylene glycol 1000 succinate (tpgs) and peg 400 as p-gp inhibitors on the intestinal absorption of etoposide. everted sacs of rat smal...