A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents
A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents
复制标题
新型CB受体GPR55及其配体参与啮齿动物肠道运动的调节
DOI：
10.1111/j.1365-2982.2011.01742.x
复制
发表时间：
2011-09-01
影响因子：
3.5
通讯作者：
Storr, M.
中科院分区：
文献类型：
--
作者：
Lin, X. -H.;Yuece, B.;Storr, M.
本研究旨在探讨新型大麻素受体G蛋白偶联受体55（GPR 55）及其配体O-1602和大麻二酚（CBD）对啮齿类动物胃肠运动的影响。方法采用内毒素（LPS）复制感染性肠梗阻模型。在O-1602或CBD存在下，通过记录大鼠空肠的肌电活动和通过用炭标记物测量小鼠的GI转运来测量肠运动。炎症反应进行了血清学和组织学评估。采用实时荧光定量PCR和免疫组织化学方法检测GPR 55在大鼠肠道不同部位的表达和分布。在离体条件下，通过测定肠肌条在器官浴中的收缩和微电极技术测定肠肌细胞内反应，研究药物对胃肠运动的影响。关键结果G蛋白偶联受体55在大鼠肠道的不同部位表达。脂多糖显著抑制肠运动，增加炎性细胞因子和GPR 55的表达。CBD预处理使LPS诱导的运动功能低下正常化，并在血清学和组织学上改善了炎症反应。O-1602和CBD都抵消了LPS诱导的肠道收缩障碍，但对肌细胞的膜电位没有影响，而大麻素1型受体拮抗剂AM 251和大麻素2型受体拮抗剂AM 630则增加了电位。结论与推论G蛋白偶联受体55存在于大鼠整个肠道。O-1602或CBD选择性地使运动障碍正常化。其作用机制可能与全身抗炎和调节肠道肌电活动有关。
Background This study was to investigate the effects of the novel cannabinoid receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. Methods Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O-1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real-time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique. Key Results G protein-coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS-induced hypomotility and improved the inflammatory responses serologically and histologically. Both O-1602 and CBD counteracted LPS-induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential. Conclusions & Inferences G protein-coupled receptor 55 existed throughout the whole intestine of rats. O-1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti-inflammation and the regulation of myoelectrical activity of the intestine.