Lindovsky_2012_Eur.J.Pharmacol_688_22

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Title : Effect of tissue-specific acetylcholinesterase inhibitor C-547 on alpha3beta4 and alphabetaepsilondelta acetylcholine receptors in COS cells - Lindovsky_2012_Eur.J.Pharmacol_688_22
Author(s) : Lindovsky J , Petrov KA , Krusek J , Reznik VS , Nikolsky EE , Vyskocil F
Ref : European Journal of Pharmacology , 688 :22 , 2012
Abstract : The C-547 is the most effective muscle and tissue-specific anticholinesterase among alkylammonium derivatives of 6-methyluracil (ADEMS) acting in nanomolar concentrations on locomotor muscles but not on respiratory muscles, smooth muscles and heart and brain acetylcholine esterases (AChE). When applied systematically it could influence peripheral acetylcholine receptors. The aim of the present study was to investigate the effect of C-547 on rat alpha3beta4 (ganglionic type) and alphabetaepsilondelta (muscle type) nicotinic receptors expressed in COS cells. Currents evoked by rapid application of acetylcholine or nicotine were recorded in whole-cell mode by electrophysiological patch-clamp technique 2-4 days after cell transfection by plasmids coding the alpha3beta4 or alphabetaepsilondelta combination of receptor subunits. In cells sensitive to acetylcholine, the application of C-547 evoked no responses. When acetylcholine was applied during an already running application of C-547, acetylcholine responses were only inhibited at concentrations higher than 10(-7)M. This inhibition is not voltage-dependent, but is accompanied by an increased rate of desensitization. Thus in both types of receptors, effective doses are approximately 100 times higher than those inhibiting AChE in leg muscles and similar to those inhibiting respiratory diaphragm muscles and external intercostal muscles. These observations show that C-547 can be considered for symptomatic treatment of myasthenia gravis and other congenital myasthenic syndromes as an inhibitor of AChE in leg muscles at concentrations much lower than those inhibiting muscle and ganglion types of acetylcholine receptors.
ESTHER : Lindovsky_2012_Eur.J.Pharmacol_688_22
PubMedSearch : Lindovsky_2012_Eur.J.Pharmacol_688_22
PubMedID: 22634638

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Citations formats

Lindovsky J, Petrov KA, Krusek J, Reznik VS, Nikolsky EE, Vyskocil F (2012)
Effect of tissue-specific acetylcholinesterase inhibitor C-547 on alpha3beta4 and alphabetaepsilondelta acetylcholine receptors in COS cells
European Journal of Pharmacology 688 :22

Lindovsky J, Petrov KA, Krusek J, Reznik VS, Nikolsky EE, Vyskocil F (2012)
European Journal of Pharmacology 688 :22