Effects of Ginger Constituents on the Gastrointestinal Tract: Role of Cholinergic M3 and Serotonergic 5-HT3 and 5-HT4 Receptors

The herbal drug ginger (Zingiber officinale Roscoe) may be effective for treating nausea, vomiting, and gastric hypomotility. In these conditions, cholinergic M-3 receptors and serotonergic 5-HT3 and 5-HT4 receptors are involved. The major chemical constituents of ginger are [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol. We studied the interaction of [6]-gingerol, [8]-gingerol, [10]-gingerol (racemates), and [6]-shogaol with guinea pig M-3 receptors, guinea pig 5-HT3 receptors, and rat 5-HT4 receptors. In whole segments of guinea pig ileum (bioassay for contractile M-3 receptors), [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol slightly but significantly depressed the maximal carbachol response at an antagonist concentration of 10 mu M. In the guinea pig myenteric plexus preparation (bioassay for contractile 5-HT3 receptors), 5-HT maximal responses were depressed by [10]-gingerol from 93 +/- 3% to 65 +/- 6% at an antagonist concentration of 3 mu M and to 48 +/- 3% at an antagonist concentration of 5 mu M following desensitization of 5-HT4 receptors and blockade of 5-HT1 and 5-HT2 receptors. [6]-Shogaol (3 mu M) induced depression to 61 +/- 3%. In rat esophageal tunica muscularis mucosae (bioassay for relaxant 5-HT4 receptors), [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]shogaol (2-6.3 mu M) showed no agonist effects. The maximal 5-HT response remained unaffected in the presence of the compounds. It is concluded that the efficiency of ginger in reducing nausea and vomiting may be based on a weak inhibitory effect of gingerols and shogaols at M-3 and 5-HT3 receptors. 5-HT4 receptors, which play a role in gastroduodenal motility, appear not to be involved in the action of these compounds.