Functional test of multidrug transporter activity in hippocampal-neocortical brain slices from epileptic patients.
J Neurosci Methods
; 200(2): 164-72, 2011 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-21763346
ABSTRACT
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 µM) and verapamil (40 µM) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Neocortex
/
Multidrug Resistance-Associated Proteins
/
Epilepsy
/
Hippocampus
Limits:
Humans
Language:
En
Journal:
J Neurosci Methods
Year:
2011
Document type:
Article
Affiliation country:
Alemania
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS