每天最新传奇SF资源,更新内容包含:超变单职业,变态单职业,超变单职业传奇,变态单职业传奇私服,变态单职业传奇,单职业传奇私服网站  

2016.11.4 广告位置出租

今日新开传奇网站-靶向外周CB1受体通过肠

作者:超变单职业_变态单职业_超变单职业传奇_就来新开单职业传奇发布网2019-07-11 20:24类型:刚开一秒传奇Sf 已有109人围观

美国国立卫生研究院的George Kunos研究组合作发现,以外周的CB1受体为靶点可以通过肠-脑信号轴减少对乙醇的摄入。相关论文发表在2019年6月出版的《Cell Metabolism》杂志上。

研究人员发现,在超变传奇私服里面,外周CB1R的反向激动剂JD5037能够减少野生型小鼠的饮酒行为,在传奇SF的游戏中,但却无法作用于CB1R、饥饿素短肽或GHS-R1A缺失的小鼠。用JD5037处理饮酒的小鼠能够抑制具有生物活性的辛酰基饥饿素生成但不影响其无活性的前体去酰基化饥饿素。在产生饥饿素的胃细胞中,JD5037通过增加脂肪酸的β-氧化,降低了来源于棕榈酰肉碱的反应底物辛酰肉碱。阻断胃部迷走神经信号的传入抑制了CB1R和GHS-R1A信号,从而降低了酒精摄入。因此,阻断饥饿素产生细胞中的CB1R能够通过抑制活化的饥饿素及其胃部迷走神经信号来降低饮酒行为。这项工作提示,阻断外周CB1R可能用于治疗酗酒行为。

据介绍,内源性大麻素(endocannabinoids)作用于大麻素-1受体(CB1R),饥饿素(ghrelin)作用其受体(GHS-R1A),这两个通路均促进寻酒行为。但这两个信号系统之间的联系却未知。

附:英文原文

Title: Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis

Author: Grzegorz Godlewski, Resat Cinar, Nathan J. Coffey, Roy G. Smith, Hiroshi Iwakura, George Kunos

Issue&Volume: Jun 04, 2019 Volume 29Issue 6

Abstract: Endocannabinoids acting on the cannabinoid-1 receptor (CB 1R) or ghrelin acting on its receptor (GHS-R 1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB 1R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB 1R, ghrelin peptide or GHS-R 1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation. Blocking gastric vagal afferents abrogated the ability of either CB 1R or GHS-R 1A blockade to reduce ethanol drinking. We conclude that blocking CB 1R in ghrelin-producing cells reduces alcohol drinking by inhibiting the formation of active ghrelin and its signaling via gastric vagal afferents. Thus, peripheral CB 1R blockade may have therapeutic potential in the treatment of alcoholism.

DOI: https://doi.org/10.1016/j.cmet.2019.04.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30196-2

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新if:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx

-Jun 04, 2019 Volume 29Issue 6

赞助本站

温馨提示如有转载或引用以上内容之必要,敬请将本文链接作为出处标注,谢谢合作!
广告位置出租