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本体感觉神经元中伸展激活通道的药理学特征分析。

Pharmacological profiling of stretch activated channels in proprioceptive neurons.

机构信息

Department of Biology and Center of Muscle Biology, University of Kentucky, Lexington, KY 40506-0225, USA.

Department of Biology and Center of Muscle Biology, University of Kentucky, Lexington, KY 40506-0225, USA.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2020 Jul;233:108765. doi: 10.1016/j.cbpc.2020.108765. Epub 2020 Apr 17.

DOI:10.1016/j.cbpc.2020.108765
PMID:32305458
Abstract

Proprioception in mammals and invertebrates occurs through stretch activated ion channels (SACs) localized in sensory endings. In mammals, the primary organs for proprioception are the intrafusal muscle spindles embedded within extrafusal muscle. In invertebrates there are varied types of sensory organs, from chordotonal organs spanning joints to muscle receptor organs (MRO) which are analogous to the mammalian muscle spindles that monitor stretch of muscle fibers. A subset of SACs are the PIEZO channels. They are comprised of a distinct type of protein sequence and are similar among species, from mammals to invertebrates. We screened several new agents (YODA 1, JEDI 2, OB 1 and DOOKU) which have been identified to act on SACs of the PIEZO 1 subtype. JEDI 2 increased activity in the crayfish MRO but not the crab chordotonal organs. The SACs of the crustacean proprioceptors have not been satisfactorily pharmacologically classified, nor has their molecular makeup been identified. We screened these pharmacological agents on model sensory organs in crustaceans to learn more about their subtype classification and compare genomic profiles of related species.

摘要

在哺乳动物和无脊椎动物中,本体感觉是通过位于感觉末梢的伸展激活离子通道(SAC)产生的。在哺乳动物中,本体感觉的主要器官是位于肌梭内的梭内肌纤维。在无脊椎动物中,有各种各样的感觉器官,从跨越关节的弦音器到类似于监测肌肉纤维伸展的哺乳动物肌梭的肌肉受体器官(MRO)。SAC 的一个子集是 PIEZO 通道。它们由一种独特的蛋白质序列组成,在从哺乳动物到无脊椎动物的物种中相似。我们筛选了几种新的药物(YODA1、JEDI2、OB1 和 DOOKU),这些药物已被确定作用于 PIEZO1 亚型的 SAC。JEDI2 增加了螯虾 MRO 的活性,但对蟹弦音器没有作用。甲壳类动物本体感受器的 SAC 尚未得到满意的药理学分类,其分子组成也尚未确定。我们在甲壳类动物的模型感觉器官上筛选了这些药物,以更多地了解它们的亚型分类,并比较相关物种的基因组图谱。

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