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Influence of P-glycoprotein on brucine transport at the in vitro blood–brain barrier
- Source :
- European Journal of Pharmacology. 690:68-76
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Brucine is a central agonist that can pass through the blood-brain barrier (BBB). The goal of this study is to examine whether brucine is one of the substrates of the drug transporter P-glycoprotein (P-gp) and to examine the effects of P-gp on the brucine transport at the in vitro BBB model. The P-gp ATPase assay was utilized to investigate the in vitro affinity of P-gp to brucine. Results suggested that K(m) of brucine (11.4 μmol/l) was smaller than the positive control, verapamil (16.4 μmol/l). In this study, we developed an in vitro BBB model, comprising a co-culture of primary rat brain microvessel endothelial cells and astrocytes for the transport study. The validated model was correct and available. Transendothelial electrical resistance reached (283.78 ± 18.85) Ω cm(2). The model displayed limited permeability to fluorescein sodium and [(125)I]albumin, with the apparent permeability coefficient Papp of (10.36 ± 0.86) × 10(-6) cm/s and (6.00 ± 0.78) × 10(-6)cm/s, respectively. The quantity of the bidirectional transport of brucine was determined by ultra-performance liquid chromatography-tandem mass spectrometry. In the absence of verapamil, the transport of brucine from basolateral compartment to apical compartment (BL-AP) was higher than from AP to BL at low, middle, and high concentrations (P
- Subjects :
- ATPase
Pharmacology
Blood–brain barrier
Rats, Sprague-Dawley
Excretion
chemistry.chemical_compound
medicine
Animals
Rhodamine 123
ATP Binding Cassette Transporter, Subfamily B, Member 1
P-glycoprotein
Brucine
biology
Albumin
Endothelial Cells
Reproducibility of Results
Biological Transport
Strychnine
Rats
medicine.anatomical_structure
chemistry
Blood-Brain Barrier
Permeability (electromagnetism)
Astrocytes
biology.protein
Verapamil
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 690
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....fb3044b18045b143ceb2958bb150c30d