Departamento de Farmacología y Nutrición, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain.
Neurogastroenterol Motil. 2010 Jun;22(6):694-e206. doi: 10.1111/j.1365-2982.2009.01466.x. Epub 2010 Feb 3.
In the absence of pathology, cannabinoid-induced depression of gastrointestinal (GI) motility is thought to be mediated primarily by CB1 receptors, whereas the role of CB2 receptors is still unclear. The aim of this work was to radiographically analyze the acute effect of the mixed cannabinoid agonist WIN 55,212-2 (WIN) on GI motor function in the rat, focusing on the involvement of CB1 and CB2 receptors.
Male Wistar rats received different doses of WIN and both psychoactivity (cannabinoid tetrad) and GI motility (radiographic analysis) were tested. The duration of WIN effect on GI motility was also radiographically analyzed. Finally, the involvement of the different cannabinoid receptors on WIN-induced alterations of GI motility was analyzed by the previous administration of selective CB1 (AM251) and CB2 (SR144528 or AM630) antagonists. After administration of contrast medium, alterations in GI motility were quantitatively evaluated in serial radiographs by assigning a compounded value to each region of the GI tract.
Low, analgesic doses of WIN delayed intestinal transit, but high, psychoactive doses were required to delay gastric emptying. Acute WIN effects on GI motility were confined to the first few hours after administration. AM251 partially counteracted the effect of WIN on GI motility. Surprisingly, SR144528 (but not AM630) enhanced WIN-induced delayed gastric emptying.
CONCLUSIONS & INFERENCES: X-ray analyses confirm that cannabinoids inhibit GI motility via CB1 receptors; in addition, cannabinoids could influence motility through interaction with a SR144528-sensitive site. Further studies are needed to verify if such site of action is the CB2 receptor.
在没有病理学的情况下，大麻素诱导的胃肠道（GI）运动抑制被认为主要是通过 CB1 受体介导的，而 CB2 受体的作用仍不清楚。本研究的目的是放射分析混合大麻素激动剂 WIN 55,212-2（WIN）对大鼠 GI 运动功能的急性影响，重点关注 CB1 和 CB2 受体的参与。
雄性 Wistar 大鼠接受不同剂量的 WIN，并测试其精神活性（大麻四氢酚）和 GI 运动（放射分析）。还放射分析了 WIN 对 GI 运动的作用持续时间。最后，通过先前给予选择性 CB1（AM251）和 CB2（SR144528 或 AM630）拮抗剂，分析不同大麻素受体在 WIN 诱导的 GI 运动改变中的参与。给药后，通过对 GI 道每个区域的复合值进行分配，在连续的射线照片中定量评估 GI 运动的变化。
低剂量的 WIN（镇痛剂量）延迟了肠道转运，但需要高剂量的 WIN（精神活性剂量）才能延迟胃排空。WIN 对 GI 运动的急性影响局限于给药后的前几个小时。AM251 部分抵消了 WIN 对 GI 运动的影响。令人惊讶的是，SR144528（而不是 AM630）增强了 WIN 诱导的胃排空延迟。
X 射线分析证实大麻素通过 CB1 受体抑制 GI 运动；此外，大麻素可能通过与 SR144528 敏感位点相互作用来影响运动。需要进一步的研究来验证该作用位点是否为 CB2 受体。
