Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China.
Neurogastroenterol Motil. 2011 Sep;23(9):862-e342. doi: 10.1111/j.1365-2982.2011.01742.x. Epub 2011 Jul 5.
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.
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.
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.
本研究旨在探讨新型大麻素受体 - G 蛋白偶联受体 55（GPR55）及其配体 O-1602 和大麻二酚（CBD）对啮齿动物胃肠道（GI）运动的影响。
体内使用脂多糖（LPS）制作脓毒症性肠梗阻模型。通过记录大鼠空肠的肌电活动，以及通过在 O-1602 或 CBD 存在的情况下用炭标记物测量小鼠的 GI 转运，来测量肠动力。通过血清学和组织学评估炎症反应。通过实时 PCR 和免疫组织化学研究 GPR55 在大鼠肠不同部位的表达和分布。在体外，通过测量肠肌条在器官浴中的收缩以及通过微电极技术测量肌细胞的细胞内反应来研究药物对 GI 运动的影响。
G 蛋白偶联受体 55 在大鼠肠的不同部位表达。脂多糖显著抑制肠动力，增加炎症细胞因子和 GPR55 表达。CBD 预处理可使 LPS 诱导的低动力正常化，并改善血清学和组织学的炎症反应。O-1602 和 CBD 均可拮抗 LPS 诱导的肠道收缩紊乱，但对肌细胞的膜电位无影响，而大麻素 1 型受体拮抗剂 AM251 和大麻素 2 型受体拮抗剂 AM630 则增加了电位。
G 蛋白偶联受体 55 存在于大鼠整个肠道中。O-1602 或 CBD 选择性地使运动障碍正常化。可能涉及全身抗炎和调节肠道肌电活动的机制。
