Linked Life Data

20688974

Source:http://linkedlifedata.com/resource/pubmed/id/20688974

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-10-20
pubmed:abstractText
Lamotrigine (LTG), an anticonvulsive drug, is often used for the treatment of a variety of epilepsies. In addition to block of sodium channels, LTG may act on other targets to exert its antiepileptic effect. In the present study, we evaluated the effects of LTG on neuronal nicotinic acetylcholine receptors (nAChRs) using the patch-clamp technique on human ?4?2-nAChRs heterologously expressed in the SH-EP1 cell line and on native ?4?2-nAChRs in dopaminergic (DA) neurons in rat ventral tegmental area (VTA). In SH-EP1 cells, LTG diminished the peak and steady-state components of the inward ?4?2-nAChR-mediated currents. This effect exhibited concentration-, voltage- and use-dependent behavior. Nicotine dose-response curves showed that in the presence of LTG, the nicotine-induced maximal current was reduced, suggesting a noncompetitive inhibition. These findings suggest that LTG inhibits human neuronal ?4?2-nAChR function through an open-channel blocking mechanism. LTG-induced inhibition in ?4?2-nAChRs was more profound when preceded by a 2-min pretreatment, after which the nicotine-induced current was reduced even without coapplication of LTG, suggesting that LTG is also able to inhibit ?4?2-nAChRs without channel activation. In freshly dissociated VTA DA neurons, LTG inhibited ?4?2-nAChR-mediated currents but did not affect glutamate- or GABA-induced currents, indicating that LTG selectively inhibits nAChR function. Collectively, our data suggest that the neuronal ?4?2-nAChR is likely an important target for mediating the anticonvulsive effect of LTG and the blockade of ?4?2-nAChR possibly underlying the mechanism through which LTG effectively controls some types of epilepsy, such as autosomal dominant nocturnal frontal lobe epilepsy or juvenile myoclonic epilepsy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
335
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The anticonvulsive drug lamotrigine blocks neuronal {alpha}4{beta}2 nicotinic acetylcholine receptors.
pubmed:affiliation
Senior Staff Scientist, Director of Neural Physiology Laboratory, Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 West Thomas Rd., Phoenix, AZ 85013-4496, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't