INVESTIGADORES
GARBUS Ingrid
congresos y reuniones científicas
Título:
Dual agonist-channel blocker activity of Lamotrigine on the nicotinic acetylcholine receptor
Autor/es:
VALLES ANA SOFIA; GARBUS INGRID,; ANTOLLINI SILVIA,; BARRANTES FRANCISCO,
Lugar:
Rosario
Reunión:
Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2006
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
DUAL AGONIST-CHANNEL BLOCKER ACTIVITY OF
LAMOTRIGINE ON THE NICOTINIC ACETYLCHOLINE
RECEPTOR
Vall¨¦s, A.S; Garbus, I; Antollini, S.S; Barrantes, F.J
UNESCO Chair Biophys. & Molec. Neurobiol./INIBIBB, 8000 B.
Blanca, Argentina.
E-mail: svalles@criba.edu.ar
Lamotrigine (LTG) is an antiepileptic drug employed in the
treatment of partial epilepsies. We studied its possible interaction
with channels other than its known therapeutic target, the voltage
gated sodium channel, using the adult muscle nicotinic
acetylcholine receptor (AChR) as a model. Patch-clamp
recordings showed that LTG (50-400 ¦ÌM) affected AChR channel
function, behaving as an open-channel blocker when co-applied
with the natural agonist, acetylcholine (Vall¨¦s et al., NeuroReport
2006, in press). Here, single-channel recordings with LTG alone
demonstrate that LTG (0.05-100 ¦ÌM) is able to activate the
AChR channel by itself. [125I]-¦Á-bungarotoxin binding studies
further indicate that LTG does not bind to the ACh binding site.
Moreover, fluorescence experiments using the probe crystal
violet, which displays higher affinity for the desensitized (D, in the
presence of agonist) than for the resting AChR conformation (R,
in the absence of agonist) show that LTG is able to induce the
transition from the R-state to the D-state in the presence of ¦Á-
bungarotoxin, i.e. when the canonical agonist binding site is
blocked. We conclude that LTG displays dual agonist /channel
blocker activities on the AChR, which operate through different
sites.