胆盐在受体激活中的作用
Frank Wolters1, Dagmar Tolenaars1, Michel van Weeghel2
1Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism (AGEM), Amsterdam University Medical Centers, the Netherlands.
概括
胆汁盐和胆红素不会通过激活已知的受体,直接引起胆固醇酶相关的. 血液中的白蛋白抑制了这些相互作用,这表明胆固醇中的间接机制正在发挥作用.
科学领域:
- 生物化学 生物化学
- 生理学 生理学 生理学
- 皮肤病学 皮肤病学
背景情况:
- 胆固醇酶相关的是一个重大的临床挑战.
- 胆汁盐和胆红素被怀疑是胆固醇酶诱导的的触发因素.
- 研究这些化合物在受体上的直接作用至关重要.
研究的目的:
- 为了确定胆汁盐和胆红素是否激活已知的受体 (TRPA1,TRPV1,TRPV3,TRPV4,MRGPRX4,TGR5).
- 评估白蛋白对这些潜在相互作用的影响.
- 为了将受体激活与胆固醇患者的强度相关联.
主要方法:
- 使用过度表达特定受体的细胞来测试通过 (Ca2+) 或cAMP信号的激活.
- 从胆固醇患者和对照组的血清中分析了受体激活.
- 血胆盐度使用HPLC-MS.量化.
主要成果:
- 结合胆汁盐与的强度相关,但大多数未结合胆汁盐没有.
- 胆汁盐和胆红素显示了TRPA1,MRGPRX4和TGR5的最小激活,这被生理性白蛋白水平废除.
- 虽然TGR5激活与相关,但在非性条件下也观察到TGR5激活,胆盐减少了白蛋白,但没有取消TGR5激活.
结论:
- 胆汁盐和胆红素在有生理性白蛋白度的情况下不会直接激活主要的感受体.
- TGR5激活与相关,但不是唯一或主要的因素.
- 这些发现表明,间接机制,而不是由胆汁盐或胆红素直接激活受体,是胆相关的的基础.
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