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XB-ART-2678
Neurosci Lett 2005 Jan 10;3732:144-9. doi: 10.1016/j.neulet.2004.10.002.
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Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite.

Sala F , Mulet J , Reddy KP , Bernal JA , Wikman P , Valor LM , Peters L , König GM , Criado M , Sala S .


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The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.

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