A novel agonist effect on the nicotinic acetylcholine receptor exerted by the anticonvulsive drug Lamotrigine

SOFIA VALLES, ANA; INGRID GARBUS; ANTOLLINI SILVIA,; BARRANTES FRANCISCO,

Biochimica et Biophysica Acta-Biomembranes

Lugar: Elsevier; Año: 2008 vol. 1778 p. 2395 - 2404

0005-2736

The anticonvulsive drug Lamotrigine (LTG) is found to activate adult muscle nicotinic acetylcholine receptors (AChR). Single-channel patch-clamp recordings showed that LTG (0.05–400 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.–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.