OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 IN THE BRAIN OF PENTYLENETETRAZOLE-KINDLED RATS

doi:10.1016/j.neuroscience.2012.10.006

	OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 IN THE BRAIN OF PENTYLENETETRAZOLE-KINDLED RATS
	Yao, D.1,2; Liu, L.2; Jin, S.2; Li, J.2; Liu, X. -D.2
刊名	NEUROSCIENCE
	2012-12-27
卷号	227 页码:283-292
关键词	multidrug resistance-associated protein 2 pharmacoresistant epilepsy phenytoin blood-brain barrier anti-epileptic effect
ISSN号	0306-4522
DOI	10.1016/j.neuroscience.2012.10.006
文献子类	Article
英文摘要	Clinical studies and animal models have shown that pharmacoresistant epilepsy is partly due to the overexpression of ATP-binding cassette transporters at the brain. The purposes of the study were to investigate the function and expression of multidrug resistance-associated protein 2 (Mrp2) in the brain of pentylenetetrazole (PTZ)-kindled rats, and the effect of the altered Mrp2 function and expression on phenytoin (PHT) distribution in the brain. Kindled rats were developed by sub-convulsive dose of PTZ (33 mg/kg, every day, intraperitoneal (i.p.)) for 28 days. Mrp2 expression and function were measured by western blot and bromosulfophthalein (BSP) distribution in the brain. PHT concentrations in the brain of PTZ-kindled rats were measured alone or with co-administration of probenecid (50 mg/kg). Further experiment was designed to investigate whether PHT treatment prevented the up-regulated brain Mrp2 expression and function induced by PTZ-kindling. The results showed that PTZ-kindling resulted in an increase of Mrp2 level in the hippocampus and cortex of rats, accompanied by significant decreases in the brain-to-plasma concentration ratio of BSP. PTZ-kindling also decreased PHT levels in the hippocampus and cortex without altering PHT concentrations in plasma, resulting in a lower brain-to-plasma concentration ratio of PHT. Co-administration of probenecid increased the brain-to-plasma ratio of BSP and PHT in the brain of both normal and PTZ-kindled rats. A 14-day PH-- treatment prevented the up-regulation of Mrp2 expression and function induced by PTZ-kindling, accompanied by increases of PHT concentrations in the brain and good anticonvulsive effects. The present study demonstrated that chronic PTZ-kindling increased Mrp2 expression and function in the rat brain, and the up-regulation partly came from epileptic seizure. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
资助项目	Project "333" of Jiangsu Province[Y092009] ; Innovative Research Team in Institution of Jiangsu Higher Education[00000000]
WOS关键词	TEMPORAL-LOBE EPILEPSY ; ANTIEPILEPTIC DRUGS ; P-GLYCOPROTEIN ; REFRACTORY EPILEPSY ; ANTICONVULSANT EFFICACY ; STATUS EPILEPTICUS ; ENDOTHELIAL-CELLS ; EXPRESSION ; PHENYTOIN ; CARBAMAZEPINE
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000312113100027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277838]
专题	中国科学院上海药物研究所
通讯作者	Liu, X. -D.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Sefety Evaluat & Res, Shanghai 201203, Peoples R China 2.China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China;
推荐引用方式 GB/T 7714	Yao, D.,Liu, L.,Jin, S.,et al. OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 IN THE BRAIN OF PENTYLENETETRAZOLE-KINDLED RATS[J]. NEUROSCIENCE,2012,227:283-292.
APA	Yao, D.,Liu, L.,Jin, S.,Li, J.,&Liu, X. -D..(2012).OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 IN THE BRAIN OF PENTYLENETETRAZOLE-KINDLED RATS.NEUROSCIENCE,227,283-292.
MLA	Yao, D.,et al."OVEREXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 IN THE BRAIN OF PENTYLENETETRAZOLE-KINDLED RATS".NEUROSCIENCE 227(2012):283-292.