The aim of the present work was to describe the distribution of lymphocyte P-glycoprotein activity on a population of healthy individuals, taking also into account sex and age. P-glycoprotein activity in lymphocytes was measured by the Rhodamine 123 efflux assay using flow cytometry, in the presence and absence of verapamil, a P-glycoprotein inhibitor. We obtained a range of P-glycoprotein acti...

The recently determined C. elegans P-glycoprotein (Pgp) structure revealed significant deviations compared to the original mouse Pgp structure, which suggested possible misinterpretations in the latter model. To address this concern, we generated an experimental electron density map from single-wavelength anomalous dispersion phasing of an original mouse Pgp dataset to 3.8 Å resolution. The map...

P-glycoprotein (P-gp), a major contributor in multidrug resistance (MDR), is a cell surface drug efflux pump restricting the intracellular accumulation of many agents used in cancer chemotherapy leading to treatment failure. Over­ expression of P-gp is a significant indicator of poor outcome in cancer including acute myelogenous leukaemia (AML). In addition to its primary drug efflux role, P-gp...

Background The human genome codes for 49 members of the large ABC protein family. Most of them are membrane transporters. The first structures of exporters have been solved in recent years. Although a remarkable achievement, some uncertainty remained with respect to the physiological conformation of the transporter, which seems not to be fully compatible with all biochemical evidence. During cr...

P-glycoprotein (P-gp) has been associated with a number of neurodegenerative diseases, including Parkinson's disease, although the mechanisms remain unclear. Altered transport of neurotoxic pesticides has been proposed in Parkinson's disease, but it is unknown whether these pesticides are P-gp substrates. We used three in vitro transport models, stimulation of ATPase activity, xenobiotic-induce...

BACKGROUND The efflux transporter P-glycoprotein, a member of the adenosine triphosphate-binding cassette superfamily, is a major determinant of the pharmacokinetics and pharmacodynamics of the opioid loperamide, a well-recognized antidiarrheal agent. Animal studies indicate that P-glycoprotein limits morphine entry into the brain. In this study, the authors examined whether other opioids of im...

Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible interactions caused by the newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylve...

Why some cancers are curable by chemotherapy while most are not is an enigma and a major challenge for cancer researchers. The use of anticancer drugs in appropriate dosages and combinations has improved response rates and prolonged life. Yet, it is not uncommon for a patient to have a relapse during a course of chemotherapy that was initially successful. The discovery more than a decade ago th...

Blood-brain barrier (BBB) P-glycoprotein activity is rapidly reduced by vascular endothelial growth factor (VEGF) acting via Src and by tumor necrosis factor-alpha acting via protein kinase C (PKC)beta1. To probe underlying mechanism(s), we developed an in vivo, immunoblot-based proteinase K (PK) protection assay to assess the changes in the P-glycoprotein content of the BBB's luminal membrane....