Bìol. Tvarin, 2016, Volume 18, Issue 2, pp. 36–44



N. Denysenko, A. Sklyarov

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Danylo Halytskyy Lviv National Medical University,
69 Pekarska str., Lviv 79010, Ukraine, zimenkovsky@meduniv.lviv.ua

Serotonin plays an important role in function regulation of the gastrointestinal tract, including the colon. We know that almost all of human body’s serotonin is synthesized and deposited in enterochromaffin cells localized in colon mucosa. Implementation of serotonin influence on smooth muscles, blood vessels and colon mucosa is performed by activating various types of serotonin receptors. 5-HT4receptors play significant role among them as they are identified on cell membranes of the colon (enterocytes, smooth muscle, endothelium).

We used mosapride citrate a 5-HT4 receptors agonistto determine their role. The study was conducted in nonlinear rats of both sexes, who were divided into 4 groups (first — intact animals,second — animals, injected 5-HT4receptors agonist, third — animals with experimental colitis, fourth — animals injected 5-HT4receptors agonist under condition of experimental colitis). Colitis was modeled by introducing a solution of acetic acid in the colon.

The colitis was accompanied by increased activity of lipid peroxidation processes, inducible NO-synthase, myeloperoxidase, which causes the development of nitrozo-oxidative stress. Mosapride action does not lead to severe morphological and biochemical changes in the colon mucosa. Activation of 5-HT4 receptors by mosaprideunder the condition of colitis reduced degree of destructive damage, content of TBA-active products, the activity of myeloperoxidase, inducible NO-synthase, superoxide dismutase and catalase in the colon mucosa, indicating a decrease of nitrozo-oxidative stress and strengthening of cytoprotection. Application of mosapride citrate has not only prokinetic effect, but also cytoprotective, antioxidant and anti-inflammatory under condition of experimental colitis.


1. Garud S., Peppercorn M. A. Ulcerative colitis: current treatment strategy and future prospects. Therapeutic Advances in Gastroenterology, 2009, 2 (2), pp. 99–108. https://doi.org/10.1177/1756283X09102329
2. De Ponti F. Pharmacology of serotonin: what a clinician should know. Gut. 2004, 53, pp. 1520–1535. https://doi.org/10.1136/gut.2003.035568
3. Goldner D., Gross-Margolis K. Association of serotonin transporter promoter polymorphism (5HTTLPR) with microscopic colitis and ulcerative colitis: time to be AsSERTive? Digestive Diseases and Sciences, 2015, 60 (4), pp. 819–821. https://doi.org/10.1007/s10620-015-3598-8
4. Gershon M. D. Review article: serotonin receptors and transporters — roles in normal and abnormal gastrointestinal motility. Alimentary Pharmacology & Therapeutics, 2004, 20 (7), pp. 3–14. https://doi.org/10.1111/j.1365-2036.2004.02180.x
5. Vento P., Kiviluoto T., Jarvinen H. J., Soinila S. Changes in distribution of three isoforms of nitric oxidesynthase in ulcerative colitis. Scandinavian Journal of Gastroenterology, 2001, 36, pp. 180–189. https://doi.org/10.1080/003655201750065942
6. Magro F., Fraga S., Azevedo I, Soares-da-Silva P. Intestinal 5-hydroxytryptamine and mast cell infiltration in rat experimental colitis. Digestive Diseases and Sciences, 2006, 51 (3), pp. 495–501. https://doi.org/10.1007/s10620-006-3161-8
7. Kruidenier L., Kuiper I., Lamers C. B., Verspage H. W. Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. The Journal of Pathology, 2003, 201 (1), pp. 28–36. https://doi.org/10.1002/path.1409
8. Muscoli C., Mollace V., Wheatley J., Masin E., Ndengele M., Wang Z. Q., Salvemini D. Superoxide-mediated nitration of spinal manganese superoxide dismutase: a novel pathway in N-methyl-D-aspartate-mediated hyperalgesia. Pain, 2004, 111 (1–2), pp. 96–103. https://doi.org/10.1016/j.pain.2004.06.004
9. Fedorak R. N., Empey L. R., MacArthur C., Jewell L. D. Misoprostol provides a colonic mucosal protective effect during acetic acid-induced colitis in rats. Gastroenterology, 1990, 98 (3), pp. 615–625. https://doi.org/10.1016/0016-5085(90)90280-E
10. Fomenko I. S., Bondarchuk T. I., Biletska L. P., Panasyuk N. B., Sklyarov O. Ya. Study of role of NO-synthase system in gastric mucosa of rats under the influence of non-steroidal anti-inflammatory drugs on the background of adrenaline-induced stress. Bulletin of problems in biology and medicin, 2013, 3, 1 (102), pp. 245–249. (in Ukrainian)
11. Ravaeva M. Yu., Chuyan E. N. Changes in activity of nitric oxide synthesis system after the action low mm radiation. Scientists Notes of Tavria National University named after V. I. Vernadsky, Series “Biology, Chemistry”, 2011, 24 (63), 4, pp. 201–210. (in Russian)
12. Korolyuk M. A., Ivanova L. I., Mayorova I. G. The method of determination of catalase activity. Laboratory Work, 1988, 1, pp. 16–19. (in Russian)
13. Goryachkovskyy A. M. Clinical Biochemistry. Second edition, corrected and updated, Odessa, 1998, pp. 368–369. (in Russian)
14. Bradley P. P., Christensen R. D., Rothstein G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood, 1982, 60, pp. 618–622.
15. Timirbulatov M. A., Seleznyov E. I. Increase intensity method of free oxidation lipidcontaining blood components and its diagnostic value. Laboratory Work, 1981, 4, pp. 209–211. (in Russian)
16. Golikov P. P., Matveev S. B., Pakhomova G. V. Dynamics of excretion of the end product of nitric oxide and nitrite excretion under conditions of peritonitis. Clinical Laboratory Services, 1999, 9, pp. 17–18. (in Russian)
17. Ruth F., Itzhaki D. M. A micro-biuret method for estimating proteins. Analytical Biochemistry, 1964, 9 (4), pp. 401–410. https://doi.org/10.1016/0003-2697(64)90200-3
18. Sklyarov A. Ya., Panasyuk N. B., Fomenko I. S. Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis. Journal of Physiology and Pharmacology, 2011, 62 (1), p. 65. (in English)
19. Fomenko I. S., Sklyarov P. O., Panasyuk N. B., Biletska L. P., Sklyarov O. Ya. Changes in activity of NO-synthase system and arginase in colon mucosa blocking inflammatory enzymes under the conditions of experimental colitis. Taurian Medical and Biology Journal. 2012, 15, 3, 1 (59), pp. 361–363. (in Ukrainian)
20. Fomenko I. S., Nasadyuk K. M., Shamro N. R., Denisenko N. V., Sklyarov A. Ya. The influence of vitamin C on the mechanisms of cytoprotection, lipoperoxidation and NO-Synthase activity in stress and experimental colitis in Rats. Modern directions in chemistry, biology, pharmacy and biotechnology. Lviv Polytechnic Publishing House, 2015, pp. 164–170.
21. Bertrand P. P., Barajas-Espinosa A., Neshat S., Bertrand R. L., Lomax A. E. Analysis of real-time serotonin (5-HT) availability during experimental colitis in mouse. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2010, 298, pp. 446–455. https://doi.org/10.1152/ajpgi.00318.2009
22. Linden D. R., Chen J. X., Gershon M. D., Sharkey K. A., Mawe G. M. Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2003, 285, pp. 207–216. https://doi.org/10.1152/ajpgi.00488.2002
23. O’Hara J. R., Ho W., Linden D. R., Mawe G. M., Sharkey K. A. Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2004, 287, pp. 998–1007. https://doi.org/10.1152/ajpgi.00090.2004
24. Bregano J. W., Barbosa D. S., El Kardi M. Z. Comparison of selective and non-selective cyclo-oxygenase 2 inhibitors in experimental colitis exacerbation: role of leukotriene B4 and superoxide dismutase. Arquivos de Gastroenterologia (Archives of Gastroenterology), 2014, 51, 3. Available at: http://www.scielo.br/scielo.php?pid=S0004-28032014000300226&script=sci_arttext. https://doi.org/10.1590/S0004-28032014000300012
25. Takaki M., Goto K., Kawahara I. The 5-hydroxitryptamine 4 receptor agonist-induced actions and enteric neurogenesis in the gut. Journal of Neurogastroenterology and Motility, 2007, 20 (1), pp. 17–30. https://doi.org/10.5056/jnm.2014.20.1.17
26. Margolis K. G., Stevanovic K., Li Z., Yang Q. M., Oravecz T., Zambrowicz B., Jhaver K. G., Diacou A., Gershon M. D. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut, 2014, 63 (6), pp. 928–937. https://doi.org/10.1136/gutjnl-2013-304901
27. Mawe G. M., Hoffman M. Serotonin signaling in the gastrointestinal tract: functions, disfunctions and therapeutic targets. Nature Reviews Gastroenterology & Hepatology, 2013, 10 (8), pp. 473–486. https://doi.org/10.1038/nrgastro.2013.105
28. Sklyarov O. Ya., Kosyy Ye. R., Sklyarov Ye. Ya. Fundamentals of Gastroenterology. Textbook. Lviv, Quartus, 2011, p. 28. (in Ukrainian)

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