A fluorinated quinuclidine benzamide named LMA 10203 acts as an agonist of insect nicotinic acetylcholine receptors

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• 作者：Monique Mathé ; -Allainmat^a ; Bé ; atrice Bodereau-Dubois^b ; Bruno Lapied^b ; Jacques Lebreton^a ; Steeve H. Thany^b ; ^{steeve.thany@univ-angers.fr}
• 关键词：Fluorinated benzamide ; Quinuclidine ; Neurons ; Nicotinic receptors ; Insect
• 刊名：Insect Biochemistry and Molecular Biology
• 出版年：2012
• 期刊代码：80_09651748
• 类别：bio
• 出版时间：June, 2012
• 卷：42
• 期：6
• 页码：417-425
• 文件大小：988 K

摘要

In the present study, we take advantage of the fact that cockroach dorsal unpaired median neurons express different nicotinic acetylcholine receptor subtypes to demonstrate that simple quinuclidine benzamides such as the 2-fluorinated benzamide LMA 10203, could act as an agonist of cockroach 伪-bungarotoxin-insensitive nicotinic acetylcholine receptor subtype, called nAChR2. Indeed, 1聽mM LMA 10203 induced ionic currents which were partially blocked by 0.5聽渭M 伪-bungarotoxin and methyllycaconitine and completely blocked by 5聽渭M mecamylamine. Moreover, the current-voltage curve revealed that the ionic current induced by LMA 10203 increased from聽鈭?0聽mV to聽+20聽mV confirming that it acted as an agonist of 伪-bungarotoxin-insensitive nAChR2. In addition, 1聽mM LMA 10203 induced a depolarization of the sixth abdominal ganglion and this neuroexcitatory activity was completely blocked by 5聽渭M mecamylamine. These data suggest that nAChR2 was also expressed at the postsynaptic level on the synapse between the cercal afferent nerve and the giant interneurons. Interestingly, despite LMA 10203 being an agonist of cockroach nicotinic receptors, it had a poor insecticidal activity. We conclude that LMA 10203 could be used as an interesting compound to identify specific insect nAChR subtypes.