We have expressed P-glycoprotein (P-gp) encoded by the mouse mdr3 gene in the yeast Saccharomyces cerevisiae and have developed an experimental protocol to isolate and purify inside-out plasma membrane vesicles (IOVs) from these cells. Biochemical characterization of IOVs from control and P-gp-expressing cells isolated by this procedure show that they are greatly enriched for plasma membrane ma...

Semen Strychni has been extensively used as a Chinese herb, but its therapeutic window is narrowed by the strong toxicity of the compound, which limits its effectiveness. Radix Paeoniae Alba has been reported to reduce the toxic effects and increase the therapeutic effects of Semen Strychni, but the underlying mechanism remains unknown. This research aimed to explore the mechanism through which...

Intestinal CYP3A and P-glycoprotein (P-gp) decrease the intestinal absorption of substrate drugs. Since substrate specificity of CYP3A often overlaps that of P-gp, and estimation of their saturability in the intestine is difficult, dose-dependent FaFg (fraction of the administered drugs that reach the portal blood) of substrate drugs and the relative importance of CYP3A and P-gp have not been c...

In machine learning, reducing the complexity of a model can help to improve its computational efficiency and avoid overfitting. genetic programming (GP), reduction is often achieved by size evolved expressions. However, previous studies have demonstrated that expression does not necessarily prevent Therefore, this paper uses evaluation time – required evaluate GP on data as estimate complexity....

The effect of atazanavir on P-glycoprotein (P-gp) expression and activity, as well as its inhibitory potency against CYP3A activity, was evaluated in vitro. Induction of P-gp activity and expression was studied using LS180V cells. P-gp inhibition was studied using both LS180V cells and Caco-2 cells. P-gp activity was assessed by measuring P-gp-mediated rhodamine 123 (Rh123) transport, and P-gp ...

To date, the in vitro–in vivo correlation (IVIVC) of P-glycoprotein (P-gp)–mediated drug-drug interaction (DDI) at the blood-brain barrier (BBB) in rats indicated that the cutoff value to significantly affect the brain penetration of digoxin was [I,unbound/Ki] of 1, where I,unbound is the unbound plasma concentration of P-gp inhibitors. On the basis of the IVIVC in rats, we speculated that clin...

P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal tubular dysfunction similar to the phenotype of patients with cystinosis, an autosoma...

This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal...

ATP-sensitive K(+) (K(ATP)) channels are the target of a number of pharmacological agents, blockers like hypoglycemic sulfonylureas and openers like the hypotensive cromakalim and diazoxide. These agents act on the channel regulatory subunit, the sulfonylurea receptor (SUR), which is an ABC protein with homologies to P-glycoprotein (P-gp). P-gp is a multidrug transporter expressed in tumor cell...

Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is a major cause of cancer therapy failure. In this study, we identified a novel C21 steroidal glycoside, asclepiasterol, capable of reversing P-gp-mediated MDR. Asclepiasterol (2.5 and 5.0μM) enhanced the cytotoxity of P-gp substrate anticancer drugs in MCF-7/ADR and HepG-2/ADM cells. MDR cells were more responsive to paclitaxel in t...