A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice.
A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice.
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DOI：
10.1016/j.neuropharm.2013.03.029
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发表时间：
2013-08
影响因子：
4.7
通讯作者：
Storr M
中科院分区：
文献类型：
--
作者：
Li K;Fichna J;Schicho R;Saur D;Bashashati M;Mackie K;Li Y;Zimmer A;Göke B;Sharkey KA;Storr M
G蛋白偶联受体55 （GPR55）是一种新型大麻素受体，其在胃肠道中的作用尚不清楚。我们研究了GPR55在胃肠道运动调节中的意义。RT-PCR和免疫组化检测GPR55 mRNA和蛋白表达。在体外和体内研究了GPR55激动剂O-1602和选择性拮抗剂大麻二酚（CBD）的作用，并与非选择性大麻素受体激动剂WIN55,212-2进行了比较。采用CB1/2−/−和GPR55−/−小鼠鉴定相关受体。GPR55定位于小鼠和人结肠的肌肠神经元上。O-1602浓度依赖性降低引起结肠肌条的收缩（约60%）和回肠肌条的弱收缩（约25%）。这些作用被CBD逆转，但CB1或CB2受体拮抗剂没有。ig和静脉注射O-1602减缓了全肠运输和结肠头排出；这些效应在GPR55−/−小鼠中不存在。WIN55,212-2减缓了全肠运输效应，在CB1拮抗剂AM251的存在下被抵消。WIN55,212-2，而不是O-1602延迟胃排空和小肠运输。运动，作为中枢镇静的标志，在WIN55,212-2治疗后减少，但O-1602治疗后没有减少。GPR55在结肠肌肠神经元上强烈表达，并选择性参与结肠运动的调节。由于GPR55受体的激活与中枢镇静无关，GPR55受体可能作为治疗结肠运动障碍的未来靶点。G蛋白偶联受体55 （GPR55）是大麻素的结合位点。没有关于GPR55在胃肠道中的功能的结论性信息。我们发现在外周或中心部位靶向GPR55会减慢胃肠道运动。GPR55激活对胃肠道运动的减缓作用主要在结肠中观察到。靶向GPR55可能是治疗结肠运动障碍的未来工具。
The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid (CB) receptor, whose role in the gastrointestinal (GI) tract remains unknown. Here we studied the significance of GPR55 in the regulation of GI motility. GPR55 mRNA and protein expression were measured by RT-PCR and immunohistochemistry. The effects of the GPR55 agonist O-1602 and a selective antagonist cannabidiol (CBD) were studied in vitro and in vivo and compared to a non-selective cannabinoid receptor agonist WIN55,212-2. CB1/2−/− and GPR55−/− mice were employed to identify the receptors involved. GPR55 was localized on myenteric neurons in mouse and human colon. O-1602 concentration-dependently reduced evoked contractions in muscle strips from the colon (∼60%) and weakly (∼25%) from the ileum. These effects were reversed by CBD, but not by CB1 or CB2 receptor antagonists. I.p. and i.c.v. injections of O-1602 slowed whole gut transit and colonic bead expulsion; these effects were absent in GPR55−/− mice. WIN55,212-2 slowed whole gut transit effects, which were counteracted in the presence of a CB1 antagonist AM251. WIN55,212-2, but not O-1602 delayed gastric emptying and small intestinal transit. Locomotion, as a marker for central sedation, was reduced following WIN55,212-2, but not O-1602 treatment. GPR55 is strongly expressed on myenteric neurons of the colon and it is selectively involved in the regulation of colonic motility. Since activation of GPR55 receptors is not associated with central sedation, the GPR55 receptor may serve as a future target for the treatment of colonic motility disorders. G protein-coupled receptor 55 (GPR55) is a binding site for cannabinoids. No conclusive information was available on function of GPR55 in the GI tract. We found that targeting GPR55 at peripheral or central sites slows GI motility. Slowing effect of GPR55 activation on GI motility is primarily observed in colon. Targeting GPR55 may be a future tool for treatment of colonic motility disorders.
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肠易激综合征 - 一种涉及肥大细胞的炎性疾病。
影响因子：
1.7
作者：
Philpott H;Gibson P;Thien F
通讯作者：
Thien F
影响因子：
4.4
作者：
Schicho, Rudolf;Storr, Martin
通讯作者：
Storr, Martin
影响因子：
7.3
作者：
Izzo, AA;Pinto, L;Capasso, F
通讯作者：
Capasso, F
影响因子：
8
作者：
Pineiro, R.;Maffucci, T.;Falasca, M.
通讯作者：
Falasca, M.
DOI：
10.1111/j.1476-5381.1957.tb01354.x
发表时间：
1957-01-01
期刊：
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子：
--
作者：
HALEY, TJ;MCCORMICK, WG
通讯作者：
MCCORMICK, WG