B. Buisson et al., The unusual nature of epibatidine responses at the alpha 4 beta 2 nicotinic acetylcholine receptor, NEUROPHARM, 39(13), 2000, pp. 2561-2569
The identification of an equatorial frog toxin, epibatidine, as a potent no
n-morphinic analgesic, selective for neuronal nicotinic acetylcholine recep
tors, provoked a marked renewal in our understanding of pain and its mechan
isms. In this work we have examined the effects of epibatidine at the major
brain rat alpha4 beta2 nicotinic acetylcholine receptor expressed in a cel
l line. Fast drug applications obtained with a modified liquid filament sys
tem were used for the analyses of the currents evoked by acetylcholine, nic
otine and epibatidine. Characterized by a slow onset and offset, epibatidin
e responses were of smaller amplitude to those evoked by acetylcholine or n
icotine. About a thousand times more sensitive to epibatidine than acetylch
oline, the alpha4 beta2 receptor also displayed a more pronounced apparent
desensitization to this compound. Finally, overnight exposure to 1 nM epiba
tidine failed to produce the functional upregulation observed with nicotine
. These data indicate that, at the rat alpha4 beta2 receptor, epibatidine a
cts as a partial agonist causing a pronounced inhibition of agonist evoked
currents at concentrations that do not activate the receptors. (C) 2000 Els
evier Science Ltd. All rights reserved.