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

[摘要]

Regulation of capacitative Ca²⁺ entry was studied in two different multidrug resistance (MDR) protein (MRP1) overexpressing cell lines, HT29^col and GLC4/ADR. MRP1 overexpression was accompanied by a decreased response to thapsigargin. 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 reduced InsP₃-mediated ⁴⁵Ca²⁺ release from intracellular stores in HT29 cells. Again, these effects were virtually abolished in HT29^col cells. Our results point to a modulatory role of MRP1 on intracellular calcium concentration ([Ca²⁺]_i) homeostasis which may contribute to the MDR phenotype.

[学科分类] 生物化学/生物物理

[关键词] Multidrug resistance protein;Capacitative Ca2+ entry;HT29 cell;GLC4 cell;MK571;D;L-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol;ABC;ATP binding cassette;[Ca2+]i;intracellular calcium concentration;MDR;multidrug resistance;MRP;multidrug resistance protein;PDMP;D;L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol