CERZOS   05458
CENTRO DE RECURSOS NATURALES RENOVABLES DE LA ZONA SEMIARIDA
Unidad Ejecutora - UE
artículos
Título:
A novel agonist effect on the nicotinic acetylcholine receptor exerted by the anticonvulsive drug Lamotrigine
Autor/es:
SOFIA VALLES, ANA; INGRID GARBUS; ANTOLLINI SILVIA,; BARRANTES FRANCISCO,
Revista:
Biochimica et Biophysica Acta-Biomembranes
Referencias:
Lugar: Elsevier; Año: 2008 vol. 1778 p. 2395 - 2404
ISSN:
0005-2736
Resumen:
The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle nicotinic acetylcholine receptors
(AChR). Single-channel patch-clamp recordings showed that LTG (0.05400 ìM) applied alone is able to open
AChR channels. [125I]á-bungarotoxin-binding studies further indicate that LTG does not bind to the canonical
ACh-binding sites. Fluorescence experiments using the probe crystal violet demonstrate that LTG induces the
transition from the resting state to the desensitized state of the AChR in the presence of excess á-
bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the openchannel
blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the
AChR through a site that is different from those of full agonists/competitive antagonists and allostericallypotentiating
ligands, respectively.400 ìM) applied alone is able to open
AChR channels. [125I]á-bungarotoxin-binding studies further indicate that LTG does not bind to the canonical
ACh-binding sites. Fluorescence experiments using the probe crystal violet demonstrate that LTG induces the
transition from the resting state to the desensitized state of the AChR in the presence of excess á-
bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the openchannel
blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the
AChR through a site that is different from those of full agonists/competitive antagonists and allostericallypotentiating
ligands, respectively.125I]á-bungarotoxin-binding studies further indicate that LTG does not bind to the canonical
ACh-binding sites. Fluorescence experiments using the probe crystal violet demonstrate that LTG induces the
transition from the resting state to the desensitized state of the AChR in the presence of excess á-
bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the openchannel
blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the
AChR through a site that is different from those of full agonists/competitive antagonists and allostericallypotentiating
ligands, respectively.á-
bungarotoxin, that is, when the agonist site is blocked. Allosterically-potentiating ligands or the openchannel
blocker QX-314 exhibited a behavior different from that of LTG. We conclude that LTG activates the
AChR through a site that is different from those of full agonists/competitive antagonists and allostericallypotentiating
ligands, respectively.