Abstract | OBJECTIVE: Pharmacoresistance is a common problem hindering treatment of epilepsy. A possible cause for this resistance is the overexpression of efflux drug transporters, e.g. P-glycoprotein (P-gp), which may decrease extracellular antiepileptic drugs levels in brains of intractable epilepsy patients. Another transmembrane drug transporter is the organic anion transporting polypeptide 2 (Oatp2), which is colocalized with P-gp in many polarized tissues. However, a role for Oatp2 in the development of multidrug resistance has not been established. In the present work, we investigated the expression of drug transporters Oatp2 and P-gp in brain, liver and kidney of rats with chronic epilepsy induced by lithium- pilocarpine. METHODS: Chronic epilepsy was elicited after status epilepticus (SE) induced by lithium- pilocarpine in adult Wistar rats. Following SE, expression of Oatp2 and P-gp protein was detected by immunohistochemistry and Western blot analysis and messenger RNA ( mRNA) using reverse transcription polymerase chain reaction (RT-PCR). Levels of the drug transporters were compared in brain, liver and kidney of chronic epileptic and control rats. RESULTS: Both Oatp2 and P-gp were expressed in the brain, liver and kidney but predominantly in the brain. In the brain, Oatp2 and P-gp immunopositive cells were observed in brain capillary endothelium and choroid plexus epithelium. Compared with control rats, Oatp2 protein expression in brain was significantly decreased, while P-gp was obviously increased in chronic epileptic rats. P-gp mRNA was also significantly higher in brains of chronic epileptic rats, whereas the expression of Oatp2 did not change. Organic anion transporting polypeptide 2 and P-gp did not change at the mRNA or protein level with epilepsy in the liver or kidney. CONCLUSIONS: Organic anion transporting polypeptide 2 and P-gp colocalized in tissues that are important in drug absorption, metabolism and excretion. Seizures seem to induce the cerebral changes of P-gp and Oatp2. However, the changes of expression of two transporters exhibit the opposite trend. Organic anion transporting polypeptide 2 might play a different role than P-gp in intractable epilepsy. Our data provide a basis for the assessment of the role of uptake transporters and efflux pumps in the development of intractable epilepsy.
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Authors | Yi Guo, Li Jiang |
Journal | Neurological research
(Neurol Res)
Vol. 32
Issue 1
Pg. 106-12
(Feb 2010)
ISSN: 1743-1328 [Electronic] England |
PMID | 19570321
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Organic Anion Transporters
- RNA, Messenger
- Slco1a4 protein, rat
- Pilocarpine
- Lithium
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(metabolism)
- Animals
- Brain
(metabolism)
- Choroid Plexus
(metabolism)
- Chronic Disease
- Endothelial Cells
(metabolism)
- Epilepsy
(chemically induced, metabolism)
- Female
- Kidney
(metabolism)
- Lithium
- Liver
(metabolism)
- Male
- Organic Anion Transporters
(metabolism)
- Pilocarpine
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Status Epilepticus
(chemically induced, metabolism)
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