| pubmed-article:8263769 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:8263769 | lifeskim:mentions | umls-concept:C0005854 | lld:lifeskim |
| pubmed-article:8263769 | lifeskim:mentions | umls-concept:C0005528 | lld:lifeskim |
| pubmed-article:8263769 | lifeskim:mentions | umls-concept:C0360714 | lld:lifeskim |
| pubmed-article:8263769 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
| pubmed-article:8263769 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:8263769 | pubmed:dateCreated | 1994-1-27 | lld:pubmed |
| pubmed-article:8263769 | pubmed:abstractText | The transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors through the blood-brain barrier was studied in vitro by using primary cultures of bovine brain capillary endothelial cells (BCEC). The uptake of HMG-CoA reductase inhibitors with the lactone form, [14C]lovastatin and [14C]simvastatin, was slightly decreased to 65% of the control uptake (37 degrees C) at low temperature (4 degrees C) and was not affected by pretreatment of the BCEC with metabolic inhibitors (2,4-dinitrophenol and rotenone). [14C]Simvastatin acid (the lactone ring-opened form) was taken up in a markedly temperature- and concentration-dependent fashion, whereas the uptake of [14C] pravastatin was negligible. At pH below 7.4, the uptake rate of [14C]simvastatin acid by the BCEC increased markedly with decreasing medium pH, whereas almost pH-independent uptake was observed in the presence of 1 mM simvastatin acid. Additional studies using an in situ rat brain perfusion method showed that the in vivo cerebrovascular permeation of [14C]simvastatin acid in rats was significantly inhibited in the presence of 1 mM simvastatin acid, demonstrating that the transport system for the acid forms of HMG-CoA reductase inhibitors functions under in vivo conditions. Several monocarboxylic acids significantly inhibited the uptake of [14C]simvastatin acid by the BCEC, whereas dicarboxylic acids did not. The uptake of [14C]simvastatin acid by the BCEC was competitively inhibited by 15 mM acetic acid. Accordingly, we concluded that HMG-CoA reductase inhibitors in lactone form are transported via simple diffusion, whereas those having an acid form are transported across the blood-brain barrier via a carrier-mediated transport mechanism for monocarboxylic acids.(ABSTRACT TRUNCATED AT 250 WORDS) | lld:pubmed |
| pubmed-article:8263769 | pubmed:language | eng | lld:pubmed |
| pubmed-article:8263769 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8263769 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:8263769 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:8263769 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:8263769 | pubmed:issn | 0022-3565 | lld:pubmed |
| pubmed-article:8263769 | pubmed:author | pubmed-author:TsujiAA | lld:pubmed |
| pubmed-article:8263769 | pubmed:author | pubmed-author:TerasakiTT | lld:pubmed |
| pubmed-article:8263769 | pubmed:author | pubmed-author:TamasSS | lld:pubmed |
| pubmed-article:8263769 | pubmed:author | pubmed-author:SahekiAA | lld:pubmed |
| pubmed-article:8263769 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:8263769 | pubmed:volume | 267 | lld:pubmed |
| pubmed-article:8263769 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:8263769 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:8263769 | pubmed:pagination | 1085-90 | lld:pubmed |
| pubmed-article:8263769 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:8263769 | pubmed:year | 1993 | lld:pubmed |
| pubmed-article:8263769 | pubmed:articleTitle | Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. | lld:pubmed |
| pubmed-article:8263769 | pubmed:affiliation | Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan. | lld:pubmed |
| pubmed-article:8263769 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:8263769 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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