Beech Robin N, Neveu Cédric
French National Institute for Agricultural Research (INRA),UR1282 Infectiologie Animale et santé Publique, Nouzilly F-37380,France.
Parasitology. 2015 Feb;142(2):303-17. doi: 10.1017/S003118201400170X. Epub 2014 Oct 30.
SUMMARY Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in post-synaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.
摘要 五聚体配体门控离子通道能迅速将突触神经递质信号转化为突触后神经元或肌肉细胞中的电反应，并控制大多数多细胞动物的神经肌肉系统。包括乙醇、尼古丁、抗抑郁药和其他情绪调节药物在内的多种药物都作用于这些受体，还有控制疼痛和运动能力的化合物，以及大多数用于控制人类和牲畜寄生虫感染的驱虫药也以这些受体为靶点。近年来，我们在理解这些受体的结构、功能、活性以及能够激活特定受体的化合物特性方面取得了重大进展。越来越明显的是，这些驱虫药靶点并非固定不变，而是在不同线虫物种之间存在显著差异。在此，我们综述关于五聚体配体门控离子通道进化的已知信息，特别关注线虫，探讨我们如何推断此类受体的起源，以及理解决定它们如何随时间变化以及在不同物种间变化的因素。利用这些知识提供了一个生物学框架，有助于理解这些重要的药物靶点，并为识别新受体和寻找新型驱虫药提供途径。
