通过粘膜释放ATP和谷氨酸酸,TRPV4刺激了结肠的 afferents
Michelle Y Meng1, Luke W Paine1, David Sagnat2
1Department of Pharmacology, University of Cambridge, Cambridge, UK.
British journal of pharmacology
|December 3, 2024
概括
在肠道粘膜中激活TRPV4通道释放ATP和谷氨酸,刺激结肠感觉神经. 准肠道粘膜可能为内脏疼痛缓解提供新的策略.
科学领域:
- 胃肠病学 胃肠病学
- 神经科学是一个神经科学.
- 疼痛研究 疼痛研究
背景情况:
- 腹部疼痛是胃肠道疾病的一个重要问题.
- 短暂受体潜在化物4 (TRPV4) 离子通道与腹痛有关.
- 在感觉神经元中有限的TRPV4表达表明非神经元参与.
研究的目的:
- 研究非神经元细胞在TRPV4介导的内脏疼痛中的作用.
- 确定结肠中TRPV4激活的机制.
- 确定潜在的治疗点对于腹痛.
主要方法:
- ex vivo 电生理学对小鼠大肠 afferent 活动.
- 生物发光检测人类和小鼠结肠中的ATP和谷氨酸释放.
- 背部根腺感觉神经元的成像.
主要成果:
- TRPV4激动剂GSK1016790A增加了结肠 afferent活动,依赖于肠道粘膜.
- GSK1016790A刺激了来自结肠组织和有机体的ATP和谷氨酸释放.
- purin 受体和谷氨酸受体对抗剂减少或消除了 afferent 响应.
结论:
- 粘膜中释放的ATP和谷氨酸会调解TRPV4诱导的结肠 afferent刺激.
- 肠道粘膜是TRPV4相关的内脏疼痛的关键参与者.
- 准肠道粘膜为内脏止痛提供了一个新的治疗途径.
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