The Activation and Inhibition of Human Nicotinic Acetylcholine Receptor by RJR-2403 Indicate a Selectivity for the alpha 4 beta 2 Receptor Subtype

• Published in: Journal of neurochemistry 2000-07, Vol.75 (1), p.204-216
• Main Authors: Papke, R L, Webster, J C, Lippiello, P M, Bencherif, M, Francis, M M
• Format: Article
• Language: English
• Subjects: Xenopus
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.2000.0750204.x

Human nicotinic acetylcholine (ACh) receptor subtypes expressed in Xenopus oocytes were characterized in terms of their activation by the experimental agonist RJR-2403. Responses to RJR-2403 were compared with those evoked by ACh and nicotine. These agonists were also characterized in terms of whether application of the drugs had the effect of producing a residual inhibition that was manifest as a decrease in subsequent control responses to ACh measured 5 min after the washout of the drug. For the activation of alpha 4 beta 2 receptors, RJR-2403 had an efficacy equivalent to that of ACh and was more potent than ACh. RJR-2403 was less efficacious than ACh for other human receptor subtypes, suggesting that it is a partial agonist for all these receptors. Nicotine activated peak currents in human alpha 4 beta 2 and alpha 3 beta 2 receptors that were 85 and 50% of the respective ACh maximum responses. Nicotine was an efficacious activator of human alpha 7 receptors, with a potency similar to ACh, whereas RJR-2403 had very low potency and efficacy for these receptors. At concentrations of