Van Sickle M D, Oland L D, Ho W, Hillard C J, Mackie K, Davison J S, Sharkey K A
Neuroscience and Gastrointestinal Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Gastroenterology. 2001 Oct;121(4):767-74. doi: 10.1053/gast.2001.28466.
BACKGROUND & AIMS: Marijuana and other cannabinoids are effective anti-emetics. Despite ongoing controversy over their usage, the receptor distribution and the site of the anti-emetic action of these compounds are not known. Our aim was to investigate whether the cannabinoid 1 receptor (CB1r) and endocannabinoids play a role in the anti-emetic action of cannabinoids.
Ferrets were given an emetic stimulus and the number of episodes of retching and vomiting were observed after administration of CB1r agonists and a CB1r antagonist. CB1r and fatty acid amide hydrolase (FAAH), which degrades endocannabinoids, were localized by immunohistochemistry.
CB1r and FAAH were localized in the dorsal vagal complex, consisting of the area postrema, nucleus of the solitary tract, and the dorsal motor nucleus of the vagus in the brainstem. CB1r was found in the myenteric plexus of the stomach and duodenum. Activation of CB1r by the agonists (delta)(9)-tetrahydrocannabinol, WIN 55,212-2, and methanandamide inhibited emesis and their action was reversed by a selective CB1r antagonist, which alone had no effect, but potentiated vomiting in response to an emetic stimulus.
CB1r mediates the anti-emetic action of cannabinoids in the dorsal vagal complex. Endocannabinoids are a novel neuroregulatory system involved in the control of emesis.
大麻及其他大麻素是有效的止吐药。尽管其使用一直存在争议，但这些化合物的受体分布及止吐作用位点尚不清楚。我们的目的是研究大麻素1受体（CB1r）和内源性大麻素是否在大麻素的止吐作用中发挥作用。
给雪貂施以催吐刺激，在给予CB1r激动剂和一种CB1r拮抗剂后，观察干呕和呕吐发作的次数。通过免疫组织化学对降解内源性大麻素的CB1r和脂肪酸酰胺水解酶（FAAH）进行定位。
CB1r和FAAH定位于迷走背侧复合体，该复合体由脑干中的最后区、孤束核和迷走神经背运动核组成。在胃和十二指肠的肌间神经丛中发现了CB1r。激动剂Δ⁹-四氢大麻酚、WIN 55,212-2和甲磺酰胺激活CB1r可抑制呕吐，其作用可被一种选择性CB1r拮抗剂逆转，该拮抗剂单独使用无作用，但可增强对催吐刺激的呕吐反应。
CB1r介导大麻素在迷走背侧复合体中的止吐作用。内源性大麻素是参与呕吐控制的一种新型神经调节系统。
