Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats

Aim: 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 concentrationdependent
manner after incubation with CJX1 and CJX2 at 1, 2.5, 5, and 10
mol/L (P<0.01), but no accumulation of Rh123 was observed in human umbilical
vein endothelial cells after incubation with CJX1 and CJX2 10 mol/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 mol/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 mol/L from the medium.
Conclusion: CJX1 and CJX2
exhibited a potent effect in the inhibition of P-gp function in vitro.