Linked Life Data

12684544

Source:http://linkedlifedata.com/resource/pubmed/id/12684544

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-19
pubmed:abstractText
The role of rat organic anion transporter 3 (rOat3; Slc22a8) in the efflux transport at the blood-brain barrier (BBB) was characterized. The expression of rOat1, rOat2, and rOat3 in the brain capillary endothelial cells (BCEC) was examined using reverse transcription-polymerase chain reaction analysis, which showed that there was no expression of rOat1 or rOat2, but moderate expression of rOat3. The expression of rOat3 in the BCEC was further confirmed by Western blotting. Immunohistochemical staining showed that rOat3 is located on the abluminal and, possibly, luminal membrane of the BCEC. The contribution of rOat3 to the efflux of para-aminohippuric acid (PAH) and benzylpenicillin (PCG), substrates of rOat3, from the cerebrum into the blood circulation across the BBB was evaluated using the Brain Efflux Index method. PAH and PCG were eliminated from the cerebrum with rate constants of 0.039 and 0.043 min-1, respectively, and the elimination was saturated at high substrate concentrations. Taking account of the dilution in the brain, the Km values for the elimination of PAH and PCG were estimated to be 168 and 29 micro M, respectively. The efflux of PAH and PCG across the BBB was inhibited in a dose-dependent manner by unlabeled PCG and PAH, respectively. The Ki value of PAH for the efflux of PCG was 106 micro M and that of PCG for the efflux of PAH was 58 micro M. These values were comparable with their Km values, suggesting that they share the same efflux mechanism at the BBB. Furthermore, cimetidine and pravastatin, which are also substrates and inhibitors of rOat3, significantly inhibited the efflux of PAH and PCG from the cerebrum. These results suggest that rOat3 is responsible for the elimination of PAH and PCG from the brain across the BBB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
306
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12684544-Animals, pubmed-meshheading:12684544-Biological Transport, pubmed-meshheading:12684544-Blood-Brain Barrier, pubmed-meshheading:12684544-Blotting, Western, pubmed-meshheading:12684544-Brain, pubmed-meshheading:12684544-Capillaries, pubmed-meshheading:12684544-Cimetidine, pubmed-meshheading:12684544-Drug Interactions, pubmed-meshheading:12684544-Enzyme Inhibitors, pubmed-meshheading:12684544-Immunohistochemistry, pubmed-meshheading:12684544-Male, pubmed-meshheading:12684544-Organic Anion Transporters, Sodium-Independent, pubmed-meshheading:12684544-Penicillin G, pubmed-meshheading:12684544-Pravastatin, pubmed-meshheading:12684544-Rats, pubmed-meshheading:12684544-Rats, Sprague-Dawley, pubmed-meshheading:12684544-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12684544-Time Factors, pubmed-meshheading:12684544-Tritium, pubmed-meshheading:12684544-p-Aminohippuric Acid
pubmed:year
2003
pubmed:articleTitle
Contribution of organic anion transporter 3 (Slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood-brain barrier.
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't