Linked Life Data

8263769

Source:http://linkedlifedata.com/resource/pubmed/id/8263769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-1-27
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)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1085-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8263769-Acetic Acid, pubmed-meshheading:8263769-Acetic Acids, pubmed-meshheading:8263769-Animals, pubmed-meshheading:8263769-Biological Transport, pubmed-meshheading:8263769-Blood-Brain Barrier, pubmed-meshheading:8263769-Brain, pubmed-meshheading:8263769-Carbon Radioisotopes, pubmed-meshheading:8263769-Cattle, pubmed-meshheading:8263769-Cells, Cultured, pubmed-meshheading:8263769-Endothelium, Vascular, pubmed-meshheading:8263769-Hydrogen-Ion Concentration, pubmed-meshheading:8263769-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:8263769-Lovastatin, pubmed-meshheading:8263769-Male, pubmed-meshheading:8263769-Perfusion, pubmed-meshheading:8263769-Pravastatin, pubmed-meshheading:8263769-Rats, pubmed-meshheading:8263769-Rats, Wistar, pubmed-meshheading:8263769-Sensitivity and Specificity, pubmed-meshheading:8263769-Simvastatin, pubmed-meshheading:8263769-Temperature
pubmed:year
1993
pubmed:articleTitle
Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier.
pubmed:affiliation
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't