Division of Gastroenterology, Department of Medicine, Snyder Institute of Infection, Immunity and Inflammation (III), Alberta, Canada.
Neurogastroenterol Motil. 2009 Dec;21(12):1326-e128. doi: 10.1111/j.1365-2982.2009.01369.x. Epub 2009 Jul 23.
The major active ingredient of the plant Salvia divinorum, salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo. The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro, prolonged colonic propulsion and slowed upper GI transit in vivo. Salvinorin A had no effect on gastric emptying in vivo. Salvinorin A reduced veratridine-, but not forskolin-induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by kappa-opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor-binaltorphimine (KOR), AM 251 (CB(1) receptor) and AM 630 (CB(2) receptor). However, in the colon in vivo, the effects were largely mediated by KORs. The effects of SA on veratridine-mediated epithelial ion transport were inhibited by nor-binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.
该植物的主要活性成分，缬草诺林 A（SA）已被用于治疗胃肠道（GI）症状。由于 SA 对结肠功能调节的作用尚不清楚，我们的目的是研究 SA 对体外和体内小鼠结肠运动和分泌的影响。使用分离的结肠制剂研究了 SA 对 GI 运动的影响，并将其与胃和回肠制剂进行了比较。使用 Ussing 室评估了结肠上皮离子转运。此外，我们通过测量结肠推进，胃排空和上 GI 转运来研究体内的 GI 运动。SA 抑制了体外小鼠结肠，胃和回肠的收缩，延长了结肠推进并减缓了体内上 GI 转运。SA 对体内胃排空没有影响。SA 抑制了辣椒素诱导的上皮离子转运，但不抑制forskolin 诱导的上皮离子转运。SA 对体外结肠运动的影响是由κ-阿片受体（KOR）和大麻素（CB）受体介导的，因为它们被 nor-binaltorphimine（KOR），AM 251（CB1 受体）和 AM 630（CB2 受体）拮抗剂抑制。然而，在体内结肠中，这些影响主要由 KOR 介导。SA 对veratridine 介导的上皮离子转运的影响被 nor-binaltorphimine 和 AM 630 抑制。SA 减缓了体外和体内结肠的运动并影响了神经源性离子转运。由于其特定的区域作用，SA 或其衍生物可能是治疗与 GI 转运增加和腹泻相关的下 GI 疾病的有用药物。
