Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons

Neurogastroenterology and Motility

Volumn 25, Issue 5, 2013, Pages

  Walstab, J ^a   Kruger D ^b   Stark, T ^b   Hofmann, T ^b   Demir, I E ^c   Ceyhan, G O ^c   Feistel, B ^d   Schemann, M ^b   Niesler, B ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d Plantextrakt GmbH and Co KG   (Germany)

Author keywords

5 HT3 receptor; Ca2+ influx; Ligand gated ion channel; Radioligand binding; Submucous plexus

Indexed keywords

(6) GINGEROL; GINGER EXTRACT; ONDANSETRON; SEROTONIN 3 ANTAGONIST; SEROTONIN 3 RECEPTOR; SHOGAOL;

ARTICLE; AUTONOMIC NERVOUS SYSTEM; BINDING SITE; CALCIUM TRANSPORT; CANCER CHEMOTHERAPY; CANCER PATIENT; CONCENTRATION RESPONSE; GINGER; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; INTESTINE INNERVATION; LIPOPHILICITY; NERVE STIMULATION; PRIORITY JOURNAL; TISSUE PREPARATION;

CATECHOLS; FATTY ALCOHOLS; GINGER; HEK293 CELLS; HUMANS; NEURONS; PLANT EXTRACTS; RECEPTORS, SEROTONIN, 5-HT3; RECOMBINANT PROTEINS; SEROTONIN 5-HT3 RECEPTOR ANTAGONISTS; SUBMUCOUS PLEXUS;

EID: 84876744518     PISSN: 13501925     EISSN: 13652982     Source Type: Journal    
DOI: 10.1111/nmo.12107     Document Type: Article

References (40)

1. Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 2008; 46: 409-20.
2. Committee on Herbal Medicinal Products (HMPC): community herbal monograph on Zingiber officinale Roscoe, rhizoma. 04 June 2012; EMA/HMPC/749154/2010.
3. Bryer E. A literature review of the effectiveness of ginger in alleviating mild-to-moderate nausea and vomiting of pregnancy. J Midwifery Womens Health 2005; 50: e1-3.
4. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol 2006; 194: 95-9.
5. Pillai AK, Sharma KK, Gupta YK, Bakhshi S. Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr Blood Cancer 2011; 56: 234-8.
6. Ryan JL, Heckler C, Dakhil SR et al. Ginger for chemotherapy-related nausea in cancer patients: a URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients. J Clin Oncol 2009; 27: 15s. (suppl; abstr 9511).
7. Ding M, Leach M, Bradley H. The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review. Women Birth 2012; Aug 27 [Epub ahead of print].
8. Hu ML, Rayner CK, Wu KL et al. Effect of ginger on gastric motility and symptoms of functional dyspepsia. World J Gastroenterol 2011; 17: 105-10.
9. Wu KL, Rayner CK, Chuah SK et al. Effects of ginger on gastric emptying and motility in healthy humans. Eur J Gastroenterol Hepatol 2008; 20: 436-40.
10. Abdel-Aziz H, Nahrstedt A, Petereit F, Windeck T, Ploch M, Verspohl EJ. 5-HT3 receptor blocking activity of arylalkanes isolated from the rhizome of Zingiber officinale. Planta Med 2005; 71: 609-16.
11. Abdel-Aziz H, Windeck T, Ploch M, Verspohl EJ. Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. Eur J Pharmacol 2006; 530: 136-43.
12. Walstab J, Rappold G, Niesler B. 5-HT(3) receptors: role in disease and target of drugs. Pharmacol Ther 2010; 128: 146-69.
13. Qian QH, Yue W, Wang YX, Yang ZH, Liu ZT, Chen WH. Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks. Arch Pharm Res 2009; 32: 565-73.
14. Kawai T, Kinoshita K, Koyama K, Takahashi K. Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome. Planta Med 1994; 60: 17-20.
15. Yamahara J, Rong HQ, Naitoh Y, Kitani T, Fujimura H. Inhibition of cytotoxic drug-induced vomiting in suncus by a ginger constituent. J Ethnopharmacol 1989; 27: 353-5.
16. Karnovsky AM, Gotow LF, McKinley DD et al. A cluster of novel serotonin receptor 3-like genes on human chromosome 3. Gene 2003; 319: 137-48.
17. Niesler B, Frank B, Kapeller J, Rappold GA. Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene 2003; 310: 101-11.
18. Boess FG, Beroukhim R, Martin IL. Ultrastructure of the 5-hydroxytryptamine3 receptor. J Neurochem 1995; 64: 1401-5.
19. Davies PA, Pistis M, Hanna MC et al. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 1999; 397: 359-63.
20. Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 1991; 254: 432-7.
21. Walstab J, Hammer C, Bönisch H, Rappold G, Niesler B. Naturally occurring variants in the HTR3B gene significantly alter properties of human heteromeric 5-hydroxytryptamine-3A/B receptors. Pharmacogenet Genomics 2008; 18: 793-802.
22. Michel K, Zeller F, Langer R et al. Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors. Gastroenterology 2005; 128: 1317-26.
23. Walstab J, Combrink S, Brüss M, Göthert M, Niesler B, Bönisch H. Aequorin luminescence-based assay for 5-hydroxytryptamine (serotonin) type 3 receptor characterization. Anal Biochem 2007; 368: 185-92.
24. Barann M, Meder W, Dorner Z et al. Recombinant human 5-HT3A receptors in outside-out patches of HEK 293 cells: basic properties and barbiturate effects. Naunyn Schmiedebergs Arch Pharmacol 2000; 362: 255-65.
25. Combrink S, Kostanian A, Walstab J et al. Characterization of the naturally occurring Arg344His variant of the human 5-HT 3A receptor. Pharmacol Rep 2009; 61: 785-97.
26. Niesler B, Walstab J, Combrink S et al. Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E. Mol Pharmacol 2007; 72: 8-17.
27. Michel K, Michaelis M, Mazzuoli G, Mueller K, Vanden Berghe P, Schemann M. Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge. J Physiol 2011; 589: 5941-7.
28. Cheng Y, Prusoff WH. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 1973; 22: 3099-108.
29. Brady CA, Stanford IM, Ali I et al. Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors. Neuropharmacology 2001; 41: 282-4.
30. Breunig E, Michel K, Zeller F, Seidl S, Weyhern CW, Schemann M. Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. J Physiol 2007; 583: 731-42.
31. Panahi Y, Saadat A, Sahebkar A, Hashemian F, Taghikhani M, Abolhasani E. Effect of ginger on acute and delayed chemotherapy-induced nausea and vomiting: a pilot, randomized, open-label clinical trial. Integr Cancer Ther 2012; 11: 204-11.
32. Pertz HH, Lehmann J, Roth-Ehrang R, Elz S. Effects of ginger constituents on the gastrointestinal tract: role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors. Planta Med 2011; 77: 973-8.
33. Riyazi A, Hensel A, Bauer K, Geissler N, Schaaf S, Verspohl EJ. The effect of the volatile oil from ginger rhizomes (Zingiber officinale), its fractions and isolated compounds on the 5-HT3 receptor complex and the serotoninergic system of the rat ileum. Planta Med 2007; 73: 355-62.
34. Barann M, Molderings G, Brüss M, Bönisch H, Urban BW, Göthert M. Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. Br J Pharmacol 2002; 137: 589-96.
35. Jiang SZ, Wang NS, Mi SQ. Plasma pharmacokinetics and tissue distribution of [6]-gingerol in rats. Biopharm Drug Dispos 2008; 29: 529-37.
36. Yu Y, Zick S, Li X, Zou P, Wright B, Sun D. Examination of the pharmacokinetics of active ingredients of ginger in humans. Aaps J 2011; 13: 417-26.
37. Johnson PJ, Bornstein JC, Furness JB, Woollard DJ, Orrman-Rossiter SL. Characterization of 5-hydroxytryptamine receptors mediating mucosal secretion in guinea-pig ileum. Br J Pharmacol 1994; 111: 1240-4.
38. Fox A, Morton IK. An examination of the 5-HT3 receptor mediating contraction and evoked [3H]-acetylcholine release in the guinea-pig ileum. Br J Pharmacol 1990; 101: 553-8.
39. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007; 132: 397-414.
40. Kapeller J, Möller D, Lasitschka F et al. Serotonin receptor diversity in the human colon: expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E. J Comp Neurol 2011; 519: 420-32.