期刊
JOURNAL OF NEUROSCIENCE METHODS
卷 200, 期 2, 页码 164-172出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2011.06.032
关键词
P-glycoprotein; Multidrug transporters; Multidrug resistance associated protein; Pharmacoresistance; Temporal lobe epilepsy; Brain slice; Calcein
资金
- Deutsche Forschungsgemeinschaft [SFB TR3]
- Hertie Foundation
- EpiCure
About 70% of the patients suffering from temporal lobe epilepsy (TLE) are resistant to currently available antiepileptic drugs (AEDs). For them one therapeutic option to achieve seizure control is to undergo epilepsy surgery. Expression of multidrug transporters is upregulated in resected tissue specimens from TLE patients, as well as in animal models of chronic epilepsy, which might lead to altered tissue availability of AEDs and therefore contribute to drug refractoriness. Here we describe a functional test of multidrug transporter activity in brain slices from TLE patients based on intracellular accumulation of the fluorescent multidrug transporter substrate calcein and compare functional data to the expression pattern of multidrug transporters. The rate of cytosolic calcein fluorescence increase was altered by inhibitors of multidrug transport such as probenecid (400 mu M) and verapamil (40 mu M) in a subset of slices, indicating the presence of functional multidrug transport proteins in human epileptic tissue. Interestingly, there were differences between the expression pattern of multidrug transporters and their ability to remove calcein-AM. Consequently, in vitro studies on multidrug transporters should always include functional tests of their activity as expression alone is not necessarily conclusive. (C) 2011 Elsevier B.V. All rights reserved.
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