Lomerizine inhibited the function of P-glycoprotein(P-gp) without decreasing the expression of mdr1 gene and P-gp in primarily cultured rat brain microvessel endothelial cells
- VernacularTitle:洛美利嗪对大鼠脑微血管内皮细胞上P-糖蛋白活力的影响与P-gp及mdr1基因mRNA表达无关
- Author:
Yulin WU
;
Bingliang MA
;
Haojie ZHU
;
Guoqing LIU
- Publication Type:Journal Article
- Keywords:
P-glycoprotein;
Lomerizine;
rat brain microvessel endothelialcells;
flow cytometry;
transwell;
rhodamine123
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2006;11(1):45-50
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the effect of Lomerizine on the activity of P-glycorprotein (P-gp) in primary cultured rat brain microvessel endothelial cells (RBMECs). METHODS: Flow cytometry was used to study the efflux of rhodamine123 (Rh123) and expression of P-gp in RBMECs. RT-PCR was used to measure the expression in mRNA level of mdr1 gene in RBMECs. Transwell model was used to detect the influence of Lomerizine on the transport of Rh123 through RBMECs monolayer. RESULTS: Lomerizine inhibited the efflux of Rh123 in RBMECs. No changes of P-gp and mdr1 gene mRNA expression were detected in RBMECs after the treatment with 30 μmol·L-1 Lomerizine for 72 h. In the study of Transwell model, Lomerizine increased significantly the transport of Rh123 through RBMECs monolayer from upper compartments to lower compartments, and inhibited obviously the transport in reverse direction. CONCLUTION: The effect of Lomerizine on the activity of P-gp was mainly via its direct inhibitory effect on the function of P-gp in RBMECs and the transport of P-gp substrates in BBB may be affected by lomerizine.
