质子感应的GPCR,GPR68,介导酸诱导的内脏知觉
Luke W Paine1, Rohit Gupta1, James P Higham1
1Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
Cellular and molecular gastroenterology and hepatology
|November 6, 2025
概括
酸感应受体G蛋白结合受体68 (GPR68) 在结肠炎中调解疼痛. 阻止GPR68会减少酸引起的结肠传感信号,为结肠炎疼痛提供潜在的治疗点.
科学领域:
- 胃肠道学和免疫学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 局部酸化和高血糖分解通过激活酸感应受体,有助于结肠炎病理.
- G蛋白结合受体68 (GPR68),是一种质子感应受体,在免疫和树皮细胞上表达.
- 单细胞RNA测序揭示了GPR68在结肠感觉神经元中的表达,这表明它在疼痛信号传递中的作用.
研究的目的:
- 研究GPR68在酸诱导的结肠痛感中的作用.
- 确定GPR68对大肠炎病理和疼痛的贡献.
- 评估GPR68作为大肠炎相关疼痛的潜在治疗点.
主要方法:
- 在RNA测序数据的in silico分析以确认GPR68在结肠病感受体和人类结肠炎组织中的表达.
- 评估GPR68在疾病活性中的作用,使用GPR68淘汰小鼠大肠炎的酸 (DSS) 模型.
- 通过大肠 afferent 记录和背部根结节 (DRG) 神经元中的成像来评估酸引起的感觉信号.
- 使用GPR68阳性全调节剂 (Ogerin) 和抗剂 (Ogremorphin) 的药理学研究.
主要成果:
- GPR68在Trpv1+结肠恶性受体中高度表达,并在炎症性肠病组织中升级调节.
- 在DSS模型中,GPR68淘汰赛小鼠表现出减少的疾病活性.
- 基因删除或GPR68的药理对抗消除或减弱酸引起的结肠 afferent反应和DRG神经元信号.
- 删除GPR68并没有影响素引起的反应,这表明它特别参与了依赖质子的信号传递.
结论:
- GPR68是酸诱导的结肠恶感的一个关键媒介.
- GPR68在与大肠炎相关的疼痛中起着重要作用.
- GPR68是治疗大肠炎患者疼痛的有前途的治疗标.
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