MK-801 prevents overexpression of multidrug resistance protein 2 after status epilepticus.
OBJECTIVE
The aim of this study was to investigate whether NMDA receptor was involved in the upregulation of multidrug resistance protein 2 (Mrp2) expression during status epilepticus (SE).


METHODS
The alterations in the expression of Mrp2 at various time points after  SE, and the inhibition of glutamate N-methyl-D-aspartate (NMDA) receptor on Mrp2 expression in hippocampus were both tested by quantitative real-time polymerase chain reaction and western blot. Moreover, immunofluorescence was also used to analyze the impact of the NMDA receptor antagonist,  MK-801, on the distribution of Mrp2 in different brain areas.


RESULTS
The results showed that gene encoding Mrp2 was upregulated in hippocampus at 6 hours after the end of SE, and this initial increase was followed by gradual normalization. While between 3 and 72 hours after the  end of SE, the protein level of Mrp2 was upregulated in hippocampus, with the highest level emerging at 24 hours. The increment of Mrp2 gene and protein induced by SE was prevented by MK-801 at 6 and 24 hours respectively after the end of SE in the hippocampus. Moreover, immunofluorescence  showed that seizures-induced increase of Mrp2 expression was attenuated by the administration of MK-801 mainly in capillaries. Rats after SE exhibited a significant upregulation of Mrp2 in the capillary endothelial cells of the cerebral cortex, piriform cortex, and hippocampus, compared with  those in control at 24 hours after the end of SE.


CONCLUSIONS
The results indicated that the NMDA receptor plays an important role in the upregulation of Mrp2 expression in the blood-brain barrier.
Changhai Hospital, Second Military Medical University, Shanghai, China.
Yong
Y
Hao
Xunyi
X
Wu
Lan
L
Xu
Yangtai
Y
Guan
Zhen
Z
Hong
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D058256:Brain Waves / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use*; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018021:Lithium Chloride / Q000633:toxicity; D018721:Muscarinic Agonists / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010862:Pilocarpine / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D016291:Dizocilpine Maleate; D018021:Lithium Chloride; D018721:Muscarinic Agonists; D018696:Neuroprotective Agents; D010862:Pilocarpine; D012333:RNA, Messenger; D014841:von Willebrand Factor; D000097202:ATP-Binding Cassette Sub-Family B Member 4