Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats.
Multidrug transporter over-expression is considered to limit access of antiepileptic drugs to the epileptic focus region and to be one cause of intractable epilepsy. To reach further proof for this multidrug transporter hypothesis, we compared P-glycoprotein expression rates in subgroups of Wistar rats which are sensitive or resistant to the anticonvulsant effect of the antiepileptic drug phenytoin in the amygdala-kindling model of temporal lobe epilepsy. In the electrode-implanted amygdala of phenytoin-resistant rats, the area labelled for P-glycoprotein was more than twice as large than that in phenytoin-sensitive rats. The data indicate that P-glycoprotein expression levels in the kindled focus have a critical impact on the anticonvulsant response to antiepileptic drugs.
Potschka
Heidrun
H
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany. heidrun.potschka@tiho-hannover.de
Volk
Holger A
HA
Löscher
Wolfgang
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000679:Amygdala / Q000528:radiation effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000528:radiation effects; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D007696:Kindling, Neurologic / Q000187:drug effects / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012684:Sensory Thresholds / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D010672:Phenytoin