GPR35激动剂通过抑制物质P释放抑制TRPA1介导的结肠恶感受
Rohit A Gupta1, James P Higham1, Abigail Pearce1
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom.
Pain
|October 9, 2024
概括
像cromolyn和zaprinast这样的GPR35激动剂,通过抑制TRPA1-介导物质P在结肠感觉神经元中的释放,为腹部不适提供非阿片类疼痛缓解.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 腹痛管理缺乏有效的非阿片类止痛药.
- G蛋白结合受体35 (GPR35) 在结肠感觉神经元中与短暂受体潜在氨酸1 (TRPA1) 共同表达.
- 在肠道中,TRPA1调解有害机械传导和恶感.
研究的目的:
- 为了研究GPR35作为内脏止痛标.
- 确定GPR35激动剂并阐明它们的作用机制.
- 评估GPR35激动剂对腹部疼痛的治疗潜力.
主要方法:
- 在形对接模拟中识别GPR35激动剂.
- 使用cromolyn (CS) 和zaprinast在小鼠GPR35.5上进行的药理学试验.
- 在野生型和GPR35淘汰赛小鼠中评估TRPA1介导的 nociceptor激活和物质P (SP) 释放.
- 测量结肠收缩的时间.
主要成果:
- 克罗莫林和扎普里纳斯特被证实是小鼠GPR35激动剂.
- GPR35激活减弱了TRPA1介导的结肠恶感受体激活和机械敏感化.
- 这些效应依赖于GPR35并通过抑制SP释放来调解.
- 通过CS预处理,TRPA1引起的结肠收缩在依赖GPR35的方式中被消除.
结论:
- GPR35激动剂抑制TRPA1介导的物质P的释放,防止结肠 nociceptor的激活和敏感化.
- GPR35代表了一个有前途的药物标,用于非阿片类药物止痛在腹痛.
- 准GPR35为内脏疼痛管理提供了一个新的治疗策略.
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