Schrattenholz A, Pereira E F, Roth U, Weber K H, Albuquerque E X, Maelicke A
Laboratory of Molecular Neurobiology, Johannes-Gutenberg University Medical School, Mainz, Germany.
Mol Pharmacol. 1996 Jan;49(1):1-6.
Similar to the gamma-aminobutyric acidA receptor and the N-methyl-D-aspartate subtype of glutamate receptor, neuronal nicotinic acetylcholine receptors are subject to positive modulatory control by allosterically acting ligands. Exogenous ligands such as galanthamine and the neurotransmitter 5-hydroxytryptamine, when applied in submicromolar concentrations with nicotinic agonists, significantly increase the frequency of opening of nicotinic receptor channels and potentiate agonist-activated currents. Because these effects have been shown to be blocked by the monoclonal antibody FK1, they are mediated by binding sites that are located on alpha subunits of nicotinic receptors and distinct from those for acetylcholine and acetylcholine-competitive ligands. At higher concentrations, the potentiating effect of these ligands decreases and is eventually overcome by an inhibition of the agonist-induced response. The sensitizing actions of galanthamine, 5-hydroxytryptamine, and related compounds, at submicromolar concentrations, may reflect the existence of cross-talk between adjacent neuroreceptors and synapses in the central nervous system and thus suggests the formation of transiently active chemical networks in the vertebrate brain.
与γ-氨基丁酸A受体和谷氨酸受体的N-甲基-D-天冬氨酸亚型类似，神经元烟碱型乙酰胆碱受体受到变构作用配体的正向调节控制。外源性配体如加兰他敏和神经递质5-羟色胺，当与烟碱激动剂以亚微摩尔浓度共同应用时，可显著增加烟碱受体通道的开放频率并增强激动剂激活的电流。由于这些效应已被单克隆抗体FK1阻断，它们是由位于烟碱受体α亚基上且与乙酰胆碱和乙酰胆碱竞争性配体的结合位点不同的结合位点介导的。在较高浓度下，这些配体的增强作用会降低，并最终被激动剂诱导反应的抑制所克服。加兰他敏、5-羟色胺及相关化合物在亚微摩尔浓度下的致敏作用，可能反映了中枢神经系统中相邻神经受体和突触之间存在串扰，因此提示脊椎动物大脑中形成了瞬时活跃的化学网络。
