Effects of ginger constituents in the gastrointestinal tract: Role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors

The herbal drug ginger (Zingiber officinale ROSCOE, Zingiberaceae) may be effective for nausea, vomiting and gastrohypomotility. In these conditions, cholinergic M₃ receptors and serotonergic 5-HT₃ and 5-HT₄ receptors are involved. We studied the interaction of four active components of ginger, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol, with guinea pig M₃ and 5-HT₃ receptors and rat 5-HT₄ receptors. At M₃ receptors of whole segments of guinea pig ileum, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol (1–30µM) failed to evoke a rightward shift of the concentration-response curve (CRC) to carbachol. The maximal carbachol response was significantly depressed at antagonist concentrations ≥10µM. At 5-HT₃ receptors of the guinea pig myenteric plexus, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol produced no rightward shift of the CRC to 5-HT at concentrations not interfering with M₃ receptors (1–6.3µM). The maximal 5-HT response was significantly depressed at antagonist concentrations ≥3µM. At 5-HT₄ receptors of rat oesophageal tunica muscularis mucosae, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol (2–6.3µM) had no agonist effect by themselves. Only [8]-gingerol produced a slight but significant rightward shift of the CRC to 5-HT. The maximal 5-HT response remained unaffected in the presence of ginger constituents. 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 M3 and 5-HT₃ receptors. 5-HT₄ receptors, which play a role in gastroduodenal motility, appear not to be involved in the action of these constituents.