大脑组胺通过基底前脑胆性神经元,腺A2B受体和老鼠的迷走神经改善结肠的超透性
Masatomo Ishioh1, Tsukasa Nozu2, Saori Miyagishi3
1Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan.
Biochemical pharmacology
|April 12, 2024
概括
大脑胺,而不是外围胺,通过H1受体,基础前脑胆固醇神经元和迷走神经来调节肠道屏障功能. 这种中心机制可能为诸如痴呆症和IBS之类的肠漏性疾病提供新的治疗点.
科学领域:
- 神经胃肠病学 神经胃肠病学
- 肠-大脑轴研究研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 肠道屏障功能障碍 (漏肠) 与IBS和神经退行性疾病有关.
- 基本前脑胆能神经元 (BFCN) 通过丁酸盐,素,腺A2B信号传递和迷走神经来调节肠道屏障功能.
- 中枢组胺在肠道屏障调节中的作用仍然未被探索.
研究的目的:
- 调查大脑组胺在调节肠道屏障功能的参与和功能.
- 阐明通过中央组胺影响肠道透性的信号通路.
主要方法:
- 在老鼠中使用埃文斯蓝色量化评估结肠透性.
- 中心 (内) 和外围 (皮下) 处方的基因组胺.
- 使用SKF91488 (希斯胺N-甲基转移酶抑制剂) 调节内源性脑胺水平.
- 利用受体对抗剂 (非尼拉胺,拉尼蒂丁,皮伦泽平) 和阴道切割来探测信号通路.
主要成果:
- 内胺和脑胺升高改善了脂聚糖 (LPS) 诱导的结肠透性.
- 中央组胺的作用是由H1受体,BFCN,腺A2B信号传递和迷走神经介导的.
- 中枢组胺对肠道屏障功能的作用与外围组胺在IBS中的作用不同.
结论:
- 脑组胺通过涉及H1受体,BFCN,腺A2B信号传递和迷路的途径中心调节肠道屏障功能.
- 这种中央组合胺通路受到丁酸盐的影响,与IBS中外围组合胺的炎症作用不同.
- 中央组胺代表了潜在的治疗点,用于泄漏性肠道相关的疾病,如痴呆症和IBS.
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