Possible Interaction: Glutathione and Verapamil

“ GSH efflux mediated by MRP1 can be stimulated by verapamil.”

“In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells.”

“We recently reported that the calcium channel blocker verapamil can activate massive GSH efflux in MRP1‐overexpressing cells, leading to cell death through apoptosis.”

“ Verapamil treatment of these cells also resulted in significant depletion of cellular GSH.”

“We found that verapamil significantly depleted cellular GSH.”

“The flexibility of that loop and the binding of a CS agent like verapamil could favor a particular conformation for the massive transport of GSH , not related to other transport activities of MRP1.”

“Depending on their nature the selected compounds have different effects, e.g. at 40 microM, verapamil inhibits 50% of DNR efflux whereas GSH efflux is increased about two-fold.”

“ Verapamil and cyclosporin A, blockers of the multidrug resistance-associated protein, decreased UVA-induced GSH efflux.”

“However, verapamil strongly stimulated MRP1-mediated GSH uptake by membrane vesicles in a concentration-dependent and osmotically sensitive manner that was inhibitable by MRP1-specific monoclonal antibodies.”

“We found that verapamil inhibited LTC(4) transport into inside-out membrane vesicles prepared from MRP1-transfected cells in a competitive manner, but only in the presence of reduced glutathione ( GSH ) or its nonreducing S-methyl derivative.”

“ Verapamil modulated DOX resistance in HL‐60‐R incompletely but, in the presence of glutathione depletion , nearly completely reversed DOX resistance.”

“ Verapamil enhanced GSH efflux, whereas ATP decreased GSH efflux.”

“An injection of verapamil at a dose of 15 mg/kg body weight but not at 5 mg/kg significantly decreased hepatic glutathione contents in both fed and fasted animals 6 h after the injection.”

“The administration of verapamil at a dose of 10 mg/kg twice a day for a week brought a significant decrease in hepatic glutathione contents and a significant increase in plasma glutathione levels.”