Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats.
OBJECTIVE
To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC).


METHODS
Isolated RBMEC were cultured in DMEM/F12 (1:1) medium. The amount of intracellular rhodamine (Rh123) was determined, using a fluorescence spectrophotometer, to evaluate the function of P-gp.


RESULTS
The accumulation of Rh123 in RBMEC was potentiated in a concentration-dependent manner after incubation with CJX1 and CJX2 at 1, 2.5, 5, and 10 micromol/L (P<0.01), but no accumulation of Rh123 was observed in human umbilical vein endothelial cells after incubation with CJX1 and CJX2 10 micromol/L (P>0.05). Accumulation of intracellular Rh123 was increased and efflux of intracellular Rh123 was decreased in a time-dependent manner from 0-100 min after CJX1 and CXJ2 at 10 micromol/L treatment. The inhibitory effect of CJX1 and CJX2 on P-gp function was reversible and remained even at 120 min after removal of CJX1 and CJX2 at 2.5 micromol/L from the medium.


CONCLUSIONS
CJX1 and CJX2 exhibited a potent effect in the inhibition of P-gp function in vitro.
Ji
Bian-Sheng
BS
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009,China.
He
Ling
L
Liu
Guo-Qing
GQ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017311:Amlodipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply; D002121:Calcium Channel Blockers / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051381:Rats; D020112:Rhodamine 123 / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C504653:CJX1, amlodipine derivative; D002121:Calcium Channel Blockers; D017311:Amlodipine; D020112:Rhodamine 123