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

FEBS Letters

Nelemans, Adriaan¹  Veldman, Robert Jan²  Filipeanu, Catalin M.¹  Kok, Jan Willem²  de Zeeuw, Dick¹ 

[1] Groningen University Institute for Drug Exploration (GUIDE), Department of Clinical Pharmacology, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands;Department of Physiological Chemistry, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

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;   

DOI  :  10.1016/S0014-5793(00)01585-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown