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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-7-2
pubmed:abstractText
Cumulative evidence suggests that several organic anions are actively effluxed from the brain to the blood across the blood-brain barrier (BBB). We examined the possibility of the presence of primary active transporters for organic anions (multidrug resistance associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT)) on the BBB by measuring the ATP-dependent uptake of 2,4-dinitrophenyl-S-glutathione (DNP-SG) and leukotriene C4 (LTC4) into membrane vesicles prepared from a cell line derived from mouse brain capillary endothelial cells (MBEC4). The ATP-dependent uptake of DNP-SG into the membrane vesicles was osmotically sensitive and was also supported by GTP, but not by AMP or ADP. An ATPase inhibitor, vanadate, blocked the ATP-dependent uptake of DNP-SG. The ATP-dependent uptake process was saturable, with Km values of 0.56 and 0.22 microM, and Vmax values of 5.5 and 27.5 pmol/min/mg protein for DNP-SG and LTC4, respectively. Northern and Western blot analyses showed the expression of murine MRP but not cMOAT in MBEC4 cells. Western blot analysis of the rat cerebral endothelial cells indicated the expression of protein(s) that is detectable with MRPr1, an antibody against MRP. These results, together with previous findings that both DNP-SG and LTC4 are good ligands for MRP, suggest that MRP is responsible for the unidirectional, energy-dependent efflux of organic anions from the brain into the circulating blood across the BBB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1260-5
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Characterization of efflux transport of organic anions in a mouse brain capillary endothelial cell line.
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan.
pubmed:publicationType
Journal Article