胰岛素增强了老鼠初级感觉神经元中的酸感应离子通道电流
Zhong-Qing Xu1, Ting-Ting Liu1, Qing-Rui Qin1
1School of Pharmacy, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, People's Republic of China.
Scientific reports
|August 5, 2024
概括
胰岛素通过胰岛素受体快速增强感官神经元中的酸感应离子通道 (ASIC) 活性. 这种通过特定信号通路介导的相互作用会影响疼痛感知.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 疼痛研究 疼痛研究
背景情况:
- 胰岛素受体存在于背部根结质 (DRG) 神经元中.
- 酸感应离子通道 (ASIC) 也在DRG神经元中表达.
- 在DRG神经元中,胰岛素信号传递和ASIC之间的相互作用尚未得到充分理解.
研究的目的:
- 为了研究胰岛素对老鼠DRG神经元中ASIC的功能活性的影响.
- 阐明参与胰岛素对ASICs调节的信号通路.
- 确定外周胰岛素受体在胰岛素诱导的疼痛行为中的作用.
主要方法:
- 胰岛素应用于大鼠DRG神经元,以测量酸引起的ASIC电流.
- 使用了胰岛素受体对抗剂GSK1838705,激素激酶抑制剂拉文杜斯A和PI3K对抗剂沃特曼宁.
- 局部注射胰岛素,以诱导和评估感觉不良行为和机械过敏症.
主要成果:
- 胰岛素迅速和度依赖增强的酸引起的ASIC电流.
- 胰岛素将最大ASIC电流响应增加了46.2%±7.6%.
- 胰岛素的作用被抗剂阻断,涉及胰岛素受体,氨酸激酶和PI3K通路.
- 胰岛素激活胰岛素受体以增加酸触发的作用潜力,并加剧酸诱导的疼痛行为.
结论:
- 胰岛素/胰岛素受体信号通过氨酸激酶和PI3K通路增强ASIC的功能活性.
- ASICs是主要感官神经元中胰岛素受体信号的目标.
- 通过胰岛素激活外围胰岛素受体可以调节疼痛.
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