title: Effects of ginger constituents on the gastrointestinal tract: role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors.
abstract: 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-HT (3) and 5-HT (4) 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-HT (3) receptors, and rat 5-HT (4) 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 µM. In the guinea pig myenteric plexus preparation (bioassay for contractile 5-HT (3) receptors), 5-HT maximal responses were depressed by [10]-gingerol from 93 ± 3 % to 65 ± 6 % at an antagonist concentration of 3 µM and to 48 ± 3 % at an antagonist concentration of 5 µM following desensitization of 5-HT (4) receptors and blockade of 5-HT (1) and 5-HT (2) receptors. [6]-Shogaol (3 µM) induced depression to 61 ± 3 %. In rat esophageal tunica muscularis mucosae (bioassay for relaxant 5-HT (4) receptors), [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol (2-6.3 µM) 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-HT (3) receptors. 5-HT (4) receptors, which play a role in gastroduodenal motility, appear not to be involved in the action of these compounds.
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Berlin (Dahlem), Germany. hpertz@zedat.fu-berlin.de
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Pertz
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
authors.forename: René
authors.initials: R
authors.lastname: Roth-Ehrang
authors.forename: Sigurd
authors.initials: S
authors.lastname: Elz
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004947:Esophagus / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000502:physiology; D020939:Zingiber officinale / Q000737:chemistry*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009325:Nausea / Q000188:drug therapy; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014839:Vomiting / Q000188:drug therapy
chemical_list: D000932:Antiemetics; D002396:Catechols; D005233:Fatty Alcohols; D043587:Receptor, Muscarinic M3; D043562:Receptors, G-Protein-Coupled; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; C040115:shogaol; C007845:gingerol; C534464:8-gingerol