Open AccessModulation of P‐glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats 1
Author(s) -
JI Biansheng,
HE Ling,
LIU Guoqing
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00528.x
Subject(s) - microvessel , rhodamine 123 , p glycoprotein , umbilical vein , intracellular , efflux , incubation , chemistry , endothelial stem cell , in vitro , pharmacology , bumetanide , biochemistry , microbiology and biotechnology , endocrinology , biology , medicine , ion transporter , angiogenesis , multiple drug resistance , membrane , antibiotics
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 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 umbilical vein endothelial cells after incubation with CJX1 and CJX2 10 μmol/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 μmol/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 μmol/L from the medium. Conclusion: CJX1 and CJX2 exhibited a potent effect in the inhibition of P‐gp function in vitro .