PMID- 18048953
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20200106
IS  - 1734-1140 (Print)
IS  - 1734-1140 (Linking)
VI  - 59
IP  - 5
DP  - 2007 Sep-Oct
TI  - Effects of some new antiepileptic drugs and progabide on glucocorticoid 
      receptor-mediated gene transcription in LMCAT cells.
PG  - 531-7
AB  - Antiepileptic drugs affect endocrine and immune system activity, however, it is 
      not clear whether these effects are indirect, via interference with 
      neurotransmitters, membrane receptors and ion channels or maybe independent of 
      neuronal mechanisms. In order to shed more light on this problem, in the present 
      study, we evaluated effects of some new-generation antiepileptic drugs and 
      progabide as a GABA-mimetic on the corticosterone-induced chloramphenicol 
      acetyltransferase (CAT) activity in mouse fibroblast cells stably transfected 
      with mouse mammary tumor virus (MMTV)-CAT plasmid. Treatment of cells with 
      felbamate for five days inhibited in a concentration-dependent manner (3-100 
      microM) the corticosterone-induced reporter gene transcription. Progabide and 
      loreclezole also inhibited the corticosterone-induced CAT activity, but with 
      lower potency, and significant effects were observed at 10 to 100 microM 
      concentration. Tiagabine and stiripentol showed less potent inhibitory effect on 
      functional activity of glucocorticoid receptors (GR). In contrast, topiramate and 
      lamotrigine (3-100 microM) failed to affect the corticosterone-induced gene 
      transcription. These data indicate that some new antiepileptic drugs and 
      progabide may suppress glucocorticoid effects via the inhibition of GR-mediated 
      gene transcription. In turn, attenuation of GR function could influence 
      antiepileptic drug effect on seizures, neuronal degeneration and immune system 
      activity.
FAU - Basta-Kaim, Agnieszka
AU  - Basta-Kaim A
AD  - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish 
      Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland.
FAU - Budziszewska, Boguslawa
AU  - Budziszewska B
FAU - Leskiewicz, Monika
AU  - Leskiewicz M
FAU - Regulska, Magdalena
AU  - Regulska M
FAU - Otczyk, Magdalena
AU  - Otczyk M
FAU - Kubera, Marta
AU  - Kubera M
FAU - Jagla, Grzegorz
AU  - Jagla G
FAU - Nowak, Wojciech
AU  - Nowak W
FAU - Luszczki, Jarogniew J J
AU  - Luszczki JJ
FAU - Czuczwar, Stanislaw J
AU  - Czuczwar SJ
FAU - Lason, Wladyslaw
AU  - Lason W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Anticonvulsants)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 38C836J57Z (progabide)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Cell Line, Tumor
MH  - Chloramphenicol O-Acetyltransferase/*biosynthesis/genetics
MH  - Corticosterone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fibroblasts/enzymology
MH  - Genes, Reporter
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Receptors, Glucocorticoid/*physiology
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
MH  - gamma-Aminobutyric Acid/*analogs & derivatives/pharmacology
EDAT- 2007/12/01 09:00
MHDA- 2008/11/19 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/08/31 00:00 [received]
PHST- 2007/10/05 00:00 [revised]
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
PST - ppublish
SO  - Pharmacol Rep. 2007 Sep-Oct;59(5):531-7.