title: Functional impairment of P-glycoprotein by sodium nitroprusside pretreatment in mouse brain capillary endothelial cells.
abstract: We examined whether pretreatment of mouse brain blood vessel endothelial cell clone 4 (MBEC4) cells with sodium nitroprusside (SNP), a NO(x) 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 [(3)H]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. [(3)H]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 NO(x) functionally impairs P-gp in the in vitro blood-brain barrier model with SNP pretreatment.
authors.affiliation: College of Pharmacy, Inje University, Gimhae 621-749, Korea.
authors.forename: Han-Joo
authors.initials: HJ
authors.lastname: Maeng
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Bang
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002460:Cell Line; D003630:Daunorubicin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014750:Vincristine / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D014750:Vincristine; D000255:Adenosine Triphosphate; C507084:Abcb1b protein, mouse; D003630:Daunorubicin