PNAS:辣椒和大麻有“共同之处”!它还能“平静”肠道
2017/05/02
你可能不会认为,辣椒和大麻有很多共同之处。近日,发表在PNAS杂志上的一项研究证实,当被吃进体内后,辣椒和大麻与我们胃里的相同受体发生作用。


你可能不会认为,辣椒和大麻有很多共同之处。然而,4月24日,发表在PNAS杂志上题为“Endocannabinoid system acts as a regulator of immune homeostasis in the gut”的一项新研究发现,当被吃进体内后,它们与我们胃里的相同受体产生作用。

当你的嘴接触到红辣椒(chili pepper),你会感觉到热。从生化的角度来讲,你的感觉并没有错。因为辣椒中的辣椒素会结合一个受体,触发神经向大脑传递信号:热!研究人员在整个胃肠道中发现了这些相同的受体。具体发现过程是怎样的呢?

来自康涅狄格大学的研究人员给小鼠喂食了辣椒素,结果发现,这使得小鼠肠道中的炎症减少了。通过喂食红辣椒,研究人员真正治愈了患有1型糖尿病的小鼠。随后,他们开始调查这背后的分子水平变化。结果发现,辣椒素结合了一种称为TRPV1的受体。这种受体存在于贯穿胃肠道的特殊细胞中。当辣椒素与TRPV1后,后者会导致细胞产生花生四烯酸乙醇胺(anandamide)。

正是annabinoid让免疫系统“平静下来”。研究人员还发现,他们能够通过给小鼠直接喂食anandamide获得相同结果:使小鼠肠道“平静”下来(gut-calming)。

先前的研究表明,大脑中也含有anandamide受体(receptors for anandamide)。这些受体与大麻中的cannabinoids发生作用,使人变得兴奋。

该研究的共同通讯作者Pramod Srivastava教授说:“这些研究结果使我们能够想象免疫系统与大脑可能的‘交流’方式。Anandamide是它们共同语言中的一个‘单词’。”尽管,Srivastava和他的同事们还不知道anandamide在免疫系统和大脑之间传递信息的方式和原因,但他们发现了anandamide调节肠道的细节。

具体来说,辣椒素会与TRPV1(作用是产生更多的anandamide)和另一受体(作用是召集抑制炎症的巨噬细胞)同时发生作用。当anandamide水平增加时,巨噬细胞的数量和活性水平也会增加。这种影响遍及整个上部肠道,包括食道、胃和胰腺。

目前,科学家们正在利用小鼠研究这种影响能否作用于一些肠道疾病。该研究有望产生治疗糖尿病和结肠炎的新疗法。

参考资料:

Active ingredients in both hot peppers and cannabis calm the gut's immune system

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  • Endocannabinoid system acts as a regulator of immune homeostasis in the gut

    Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2. We show that the engagement of the cannabinoid/vanilloid receptors augments the number and immune suppressive function of the regulatory CX3CR1hi macrophages (Mϕ), which express the highest levels of such receptors among the gut immune cells. Additionally, TRPV1−/− or CB2−/− mice have fewer CX3CR1hi Mϕ in the gut. Treatment of mice with CP also leads to differentiation of a regulatory subset of CD4+ cells, the Tr1 cells, in an IL-27–dependent manner in vitro and in vivo. In a functional demonstration, tolerance elicited by engagement of TRPV1 can be transferred to naïve nonobese diabetic (NOD) mice [model of type 1 diabetes (T1D)] by transfer of CD4+ T cells. Further, oral administration of AEA to NOD mice provides protection from T1D. Our study unveils a role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and reveals a conversation between the nervous and immune systems using distinct receptors.

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