Regulation of [Ca2+](i) homeostasis in MRP1 overexpressing cells

Regulation of capacitative Ca2+ entry,vas studied in two different multidru g resistance (MDR) protein (MRP1) overexpressing cell lines, HT29(col) and GLC4/ADR. MRP1 overexpression was accompanied by a decreased response to th apsigargin, Moreover, inhibition of capacitative Ca2+ entry by D,L-threo-1- phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) was abolished in MRP1 overexpressing cells. Both PDMP and the MRP1 inhibitor MK571 greatly reduc ed InsP(3)-mediated Ca-45(2+) release from intracellular stores in HT29 cel ls. Again, these effects were virtually abolished in HT29(col) cells. Our r esults point to a modulatory role of MRP1 on intracellular calcium concentr ation ([Ca2+](i)) homeostasis which may contribute to the MDR phenotype, (C ) 2000 Federation of European Biochemical Societies.