Regulation of [Ca(2+)](i) homeostasis in MRP1 overexpressing cells.
Regulation of capacitative Ca(2+) 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 Ca(2+) 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 InsP(3)-mediated (45)Ca(2+) 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 ([Ca(2+)](i)) homeostasis which may contribute to the MDR phenotype.
Filipeanu
C M
CM
Groningen University Institute for Drug Exploration, Department of Clinical Pharmacology, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Nelemans
A
A
Veldman
R J
RJ
de Zeeuw
D
D
Kok
J W
JW
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics*; D000230:Adenocarcinoma; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D003110:Colonic Neoplasms; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D002118:Calcium; D002132:Calcium Radioisotopes; D015544:Inositol 1,4,5-Trisphosphate; D009025:Morpholines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011804:Quinolines; D019284:Thapsigargin; C059141:verlukast; C033110:RV 538