Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2006-10-23
pubmed:abstractText
Allelic variants of the human P-glycoprotein encoding gene MDR1 (ABCB1) are discussed to be associated with different clinical conditions including pharmacoresistance of epilepsy. However, conflicting data have been reported with regard to the functional relevance of MDR1 allelic variants for the response to antiepileptic drugs. To our knowledge, it is not known whether functionally relevant genetic polymorphisms also occur in the two genes (Mdr1a/Abcb1a, Mdr1b/Abcb1b) coding for P-glycoprotein in the brain of rodents. Therefore, we have started to search for polymorphisms in the Mdr1a gene, which governs the expression of P-glycoprotein in brain capillary endothelial cells in rats. In the kindling model of temporal lobe epilepsy, subgroups of phenytoin-sensitive and phenytoin-resistant rats were selected in repeated drug trials. Sequencing of the Mdr1a gene coding sequence in the subgroups revealed no general differences between drug-resistant and drug-sensitive rats of the Wistar outbred strain. A comparison between different inbred and outbred rat strains also gave no evidence for polymorphisms in the Mdr1a coding sequence. However, in exon-flanking intron sequences, four genetic variants were identified by comparison between these rats strains. In conclusion, the finding that Wistar rats vary in their response to phenytoin, while having the same genetic background, argues against a major impact of Mdr1a genetics on pharmacosensitivity to antiepileptic drugs in the amygdala kindling model.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
550
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-61
pubmed:meshHeading
pubmed-meshheading:17045987-ATP-Binding Cassette Transporters, pubmed-meshheading:17045987-Animals, pubmed-meshheading:17045987-Anticonvulsants, pubmed-meshheading:17045987-DNA Primers, pubmed-meshheading:17045987-Epilepsy, pubmed-meshheading:17045987-Exons, pubmed-meshheading:17045987-Female, pubmed-meshheading:17045987-Introns, pubmed-meshheading:17045987-Kindling, Neurologic, pubmed-meshheading:17045987-P-Glycoproteins, pubmed-meshheading:17045987-Phenytoin, pubmed-meshheading:17045987-Polymorphism, Genetic, pubmed-meshheading:17045987-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:17045987-Rats, pubmed-meshheading:17045987-Rats, Inbred Strains, pubmed-meshheading:17045987-Rats, Wistar, pubmed-meshheading:17045987-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17045987-Species Specificity
pubmed:year
2006
pubmed:articleTitle
Polymorphic variants of the multidrug resistance gene Mdr1a and response to antiepileptic drug treatment in the kindling model of epilepsy.
pubmed:affiliation
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't