Linked Life Data

10537053

Source:http://linkedlifedata.com/resource/pubmed/id/10537053

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-11-5
pubmed:abstractText
The blood-brain barrier (BBB) plays an important role in controlling the passage of molecules from the blood to the extracellular fluid environment of the brain. The multidrug efflux pump P-glycoprotein (P-gp) is highly expressed in the luminal membrane of brain capillary endothelial cells, thus forming a functional barrier to lipid-soluble drugs, notably, antitumor agents. It is of interest to develop an in vitro BBB model that stably expresses P-gp to investigate the mechanisms of regulation in expression and activity. The rat brain endothelial cell line, GPNT, was derived from a previously characterized rat brain endothelial cell line. A strong expression of P-gp was found in GPNT monocultures, whereas the multidrug resistance-associated pump Mrp1 was not expressed. The transendothelial permeability coefficient of the P-gp substrate vincristine across GPNT monolayers was close to the permeability coefficient of bovine brain endothelial cells cocultured with astrocytes, a previously documented in vitro BBB model. Furthermore, the P-gp blocker cyclosporin A induced a large increase in apical to basal permeability of vincristine. Thus, P-gp is highly functional in GPNT cells. A 1-h treatment of GPNT cells with dexamethasone resulted in decreased uptake of vincristine without any increase in P-gp expression. This effect could be mimicked by protein kinase C (PKC) activation and prevented by PKC inhibition, strongly suggesting that activation of P-gp function may involve a PKC-dependent pathway. These results document the GPNT cell line as a valuable in vitro model for studying drug transport and P-gp function at the BBB and suggest that activation of P-gp activity at the BBB might be considered in chemotherapeutic treatment of cancer patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1954-63
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10537053-Animals, pubmed-meshheading:10537053-Astrocytes, pubmed-meshheading:10537053-Blood-Brain Barrier, pubmed-meshheading:10537053-Brain, pubmed-meshheading:10537053-Cattle, pubmed-meshheading:10537053-Cell Line, Transformed, pubmed-meshheading:10537053-Cell Membrane Permeability, pubmed-meshheading:10537053-Coculture Techniques, pubmed-meshheading:10537053-Colchicine, pubmed-meshheading:10537053-Cyclosporine, pubmed-meshheading:10537053-DNA-Binding Proteins, pubmed-meshheading:10537053-Dexamethasone, pubmed-meshheading:10537053-Endothelium, Vascular, pubmed-meshheading:10537053-Glucocorticoids, pubmed-meshheading:10537053-Multidrug Resistance-Associated Proteins, pubmed-meshheading:10537053-P-Glycoprotein, pubmed-meshheading:10537053-Protein Kinase C, pubmed-meshheading:10537053-Rats, pubmed-meshheading:10537053-Rats, Sprague-Dawley, pubmed-meshheading:10537053-Vincristine
pubmed:year
1999
pubmed:articleTitle
Dexamethasone regulation of P-glycoprotein activity in an immortalized rat brain endothelial cell line, GPNT.
pubmed:affiliation
INSERM U. 26, Hôpital Fernand Widal, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't