Linked Life Data

18577448

Source:http://linkedlifedata.com/resource/pubmed/id/18577448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-11-21
pubmed:abstractText
To reach its target cells, the antiepileptic drug valproate has to cross both the intestinal epithelial barrier and the blood-brain barrier in intact form as well as in sufficient amounts. This study was performed to characterize the epithelial transport of valproate at intestinal (Caco-2) and at blood-brain barrier (RBE4) cells. At both cell types, uptake of [(3)H]valproate was independent of inwardly directed Na(+), Ca(2+), Mg(2+), K(+) or Cl(-) gradients. Uptake was, however, strongly stimulated by an inwardly directed H(+) gradient. The cells accumulated valproate against a concentration gradient and the uptake rate of valproate was saturable with K(t) values of 0.6 and 0.8mM. At Caco-2 cell monolayers, the total apical-to-basolateral flux of [(3)H]valproate exceeded the basolateral-to-apical flux 14-fold. Various monocarboxylic acids like salicylate, benzoate, acetate, propionate, butyrate, hexanoate, diclofenac and ibuprofen inhibited [(3)H]valproate uptake at both cell types. Lactate and pyruvate inhibited valproate uptake at RBE4 cells but not at Caco-2 cells. We conclude that valproate is accumulated in intestinal cells against a concentration gradient by the activity of a specific H(+)-dependent DIDS-insensitive transport system for monocarboxylates not identical with monocarboxylate transporter 1 (MCT1). The passage of valproate across the blood-brain barrier is very likely mediated by MCT1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0939-6411
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
486-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Transport of valproate at intestinal epithelial (Caco-2) and brain endothelial (RBE4) cells: mechanism and substrate specificity.
pubmed:affiliation
Biozentrum, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't