期刊
ARCHIVES OF PHARMACAL RESEARCH
卷 35, 期 7, 页码 1215-1221出版社
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-012-0712-8
关键词
P-glycoprotein; Nitric oxide forms; MBEC4; MBEC4 plasma membrane vesicles; Vincristine; Daunomycin
资金
- Inje University
We examined whether pretreatment of mouse brain blood vessel endothelial cell clone 4 (MBEC4) cells with sodium nitroprusside (SNP), a NOx donor, as an in vitro model of the bloodbrain barrier could affect P-glycoprotein (P-gp) functional activity. Uptake into the cells and MBEC4 plasma membrane vesicles (MPMVs) in the presence or absence of SNP pretreatment was used to investigate functional changes. Increased accumulation of [H-3]vincristine, a widely used substrate for P-gp, into MBEC4 was observed upon SNP pretreatment, likely due to impaired P-gp function. To better understand the mechanism of the impairment, MPMVs were prepared and characterized in terms of purity and Na+-dependent glucose uptake. [H-3]daunomycin uptake into MPMVs was diminished after SNP pretreatment in the presence of an ATP-regenerating system, indicating that the functional activity of P-gp was impaired after exposure to SNP. Under conditions of excess ATP, daunomycin uptake into the vesicles was still decreased after SNP pretreatment, indicating that SNP interacted directly with the transport system, but not with the ATP-regenerating system. Together, these results suggest that NO or NOx functionally impairs P-gp in the in vitro blood-brain barrier model with SNP pretreatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据