The unusual nature of epibatidine responses at the α4β2 nicotinic acetylcholine receptor

The identification of an equatorial frog toxin, epibatidine, as a potent non-morphinic analgesic, selective for neuronal nicotinic acetylcholine receptors, provoked a marked renewal in our understanding of pain and its mechanisms. In this work we have examined the effects of epibatidine at the major...

Full description

Saved in:
Bibliographic Details
Published inNeuropharmacology Vol. 39; no. 13; pp. 2561 - 2569
Main Authors Buisson, Bruno, Vallejo, Yolanda F, Green, William N, Bertrand, Daniel
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 01.12.2000
Elsevier
Subjects
Analgesia
Analgesics
Biological and medical sciences
Epibatidine
Medical sciences
Neuropharmacology
Nicotine
Nicotinic receptor
Pharmacology. Drug treatments
Upregulation
Epibatidine
Analgesia
Upregulation
Nicotinic receptor
Nicotine
Agonist
Rat
Rodentia
Central nervous system
Molecular interaction
Subunit
In vitro
Dose activity relation
Toxin
Alkaloid
Cholinergic receptor
Vertebrata
Mammalia
Analgesic
Animal
Acetylcholine
Mechanism of action
Brain (vertebrata)
Online AccessGet full text

Cover

More Information
Summary:The identification of an equatorial frog toxin, epibatidine, as a potent non-morphinic analgesic, selective for neuronal nicotinic acetylcholine receptors, provoked a marked renewal in our understanding of pain and its mechanisms. In this work we have examined the effects of epibatidine at the major brain rat α4β2 nicotinic acetylcholine receptor expressed in a cell line. Fast drug applications obtained with a modified liquid filament system were used for the analyses of the currents evoked by acetylcholine, nicotine and epibatidine. Characterized by a slow onset and offset, epibatidine responses were of smaller amplitude to those evoked by acetylcholine or nicotine. About a thousand times more sensitive to epibatidine than acetylcholine, the α4β2 receptor also displayed a more pronounced apparent desensitization to this compound. Finally, overnight exposure to 1 nM epibatidine failed to produce the functional upregulation observed with nicotine. These data indicate that, at the rat α4β2 receptor, epibatidine acts as a partial agonist causing a pronounced inhibition of agonist evoked currents at concentrations that do not activate the receptors.
ISSN:0028-3908
1873-7064
DOI:10.1016/S0028-3908(00)00158-1