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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:YX19781987
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Aim:To investigate whether the amlodipine derivatives,CJX1 and CJX2,havea modulative effect on P-glycoprotein(P-gp)function in rat brain microvesselendothelial cells(RBMEC).Methods:Isolated RBMEC were cultured in DMEM/F 12(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 10μmol/L(P<0.01),but no accumulation of Rh123 was observed in human umbili-cal vein endothelial cells after incubation with CJX1 and CJX2 10 μmol/L(P>0.05).Accumulation of intracellular Rh123 was increased and efflux of intra-cellular Rh123 was decreased in a time-dependent manner from 0-100 min afterCJX1 and CXJ2 at 10 ∴mol/L treatment.The inhibitory effect of CJX1 and CJX2on P-gp function was reversible and remained even at 120 min after removal ofCJX1 and CJX2 at 2.5μmol/L from the medium.Conclusion:CJX1 and CJX2exhibited a potent effect in the inhibition of P-gp function in vitro. Aim: To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P-glycoprotein (P-gp) function in rat brain microvesselendothelial cells (RBMEC). Methods: Isolated RBMEC were cultured in DMEM / F12 Results of The accumulation of Rh123 in RBMEC were potentiated in a concentration-dependent manner after incubation with CJX1 and CJX2 at 1,2,5,5 and 10 μmol / L (P <0.01), but no accumulation of Rh123 was observed in human umbili-cal vein endothelial cells after incubation with CJX1 and CJX2 10 μmol / L (P> 0.05) .Accumulation of intracellular Rh123 was increased and efflux of intra-cellular Rh123 was decreased in a time-dependent manner from 0-100 min afterCJX1 and CXJ2 at 10 mol / L treatment. The inhibitory effect of CJX1 and CJX2on P-gp function was reversible and remained even at 120 min after removal ofCJX1 and CJX2 at 2.5 μmol / L fro m the medium. Conlusion: CJX1 and CJX2 exhibited a potent effect in the inhibition of P-gp function in vitro.
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