Gene, Cell and Tissue

Published by: Kowsar

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Farzaneh Farajian Mashhadi 1 , 2 , Robert J. Naylor 3 and Farideh A. Javid 3 , *
Authors Information
1 Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, IR Iran
2 Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran
3 Department of Pharmacology, University of Bradford, Bradford, West Yorkshire, United Kingdom
Article information
  • Gene, Cell and Tissue: April 01, 2014, 1 (1); e18311
  • Published Online: March 8, 2014
  • Article Type: Research Article
  • Received: February 3, 2014
  • Revised: February 15, 2014
  • Accepted: February 17, 2014
  • DOI: 10.17795/gct-18311

To Cite: Farajian Mashhadi F, Naylor R J, Javid F A. The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine, Gene Cell Tissue. 2014 ; 1(1):e18311. doi: 10.17795/gct-18311.

Copyright © 2014, Zahedan University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Materials and Methods
4. Results
5. Discussion
  • 1. Mawe GM, Hoffman JM. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013; 10(8): 473-86[DOI][PubMed]
  • 2. Spiller R. Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease. Neurogastroenterol Motil. 2007; 19 Suppl 2: 25-31[DOI][PubMed]
  • 3. Farajian-Mashhadi F, Naylor RJ, Javid FA. The effect of fluoxetine on electrical field stimulation-induced responses in the isolated rat small intestine. Methods Find Exp Clin Pharmacol. 2010; 32(9): 645-55[DOI][PubMed]
  • 4. Molderings GJ. Physiological, pathophysiological and therapeutic impact of the enteric serotonergic system. Arzneimittelforschung. 2012; 62(4): 157-66[DOI][PubMed]
  • 5. Feldberg W, Toh CC. Distribution of 5-hydroxytryptamine (serotonin, enteramine) in the wall of the digestive tract. J Physiol. 1953; 119(2-3): 352-62[PubMed]
  • 6. Erspamer V. Pharmacology of indole-alkylamines. Pharmacol Rev. 1954; 6(4): 425-87[PubMed]
  • 7. Branchek TA, Gershon MD. Development of neural receptors for serotonin in the murine bowel. J Comp Neurol. 1987; 258(4): 597-610[DOI][PubMed]
  • 8. Kirchgessner AL, Liu MT, Raymond JR, Gershon MD. Identification of cells that express 5-hydroxytryptamine1A receptors in the nervous systems of the bowel and pancreas. J Comp Neurol. 1996; 364(3): 439-55[DOI][PubMed]
  • 9. Broad RM, McDonald TJ, Cook MA. Adenosine and 5-HT inhibit substance P release from nerve endings in myenteric ganglia by distinct mechanisms. Am J Physiol. 1993; 264(3 Pt 1)-61[PubMed]
  • 10. Pan H, Galligan JJ. 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. Am J Physiol. 1994; 266(2 Pt 1)-8[PubMed]
  • 11. Derkach V, Surprenant A, North RA. 5-HT3 receptors are membrane ion channels. Nature. 1989; 339(6227): 706-9[DOI][PubMed]
  • 12. Mawe GM, Branchek TA, Gershon MD. Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists. Proc Natl Acad Sci U S A. 1986; 83(24): 9799-803[PubMed]
  • 13. Costall B, Naylor RJ. The pharmacology of the 5-HT4 receptor. Int Clin Psychopharmacol. 1993; 8 Suppl 2: 11-8[PubMed]
  • 14. Craig DA, Clarke DE. Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor. J Pharmacol Exp Ther. 1990; 252(3): 1378-86[PubMed]
  • 15. Hume SP, Ashworth S, Opacka-Juffry J, Ahier RG, Lammertsma AA, Pike VW, et al. Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain. Eur J Pharmacol. 1994; 271(2-3): 515-23[PubMed]
  • 16. Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP. GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. Br J Pharmacol. 1994; 111(1): 332-8[PubMed]
  • 17. Hirst WD, Minton JA, Bromidge SM, Moss SF, Latter AJ, Riley G, et al. Characterization of [(125)I]-SB-258585 binding to human recombinant and native 5-HT(6) receptors in rat, pig and human brain tissue. Br J Pharmacol. 2000; 130(7): 1597-605[DOI][PubMed]
  • 18. Hagan JJ, Price GW, Jeffrey P, Deeks NJ, Stean T, Piper D, et al. Characterization of SB-269970-A, a selective 5-HT(7) receptor antagonist. Br J Pharmacol. 2000; 130(3): 539-48[DOI][PubMed]
  • 19. Weber LJ. Gastrointestinal 5-hydroxytryptamine depletion by p-chlorophenylalanine. Proc West Pharmacol Soc. 1969; 12: 128-9[PubMed]
  • 20. Kilbinger H, Kruel R, Pfeuffer-Friederich I, Wessler I. The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1982; 319(3): 231-8[PubMed]
  • 21. Nowak TV, Harrington B, Kalbfleisch JH. Evidence for muscarinic inhibitory neurotransmission in rodent small intestine. J Pharmacol Exp Ther. 1989; 248(2): 573-80[PubMed]
  • 22. Gershon MD. Effects of tetrodotoxin on innervated smooth muscle preparations. Br J Pharmacol Chemother. 1967; 29(3): 259-79[PubMed]
  • 23. Racke K, Reimann A, Schworer H, Kilbinger H. Regulation of 5-HT release from enterochromaffin cells. Behav Brain Res. 1996; 73(1-2): 83-7[PubMed]
  • 24. Satoh Y, Takeuchi T, Yamazaki Y, Okishio Y, Nishio H, Takatsuji K, et al. Mediators of nonadrenergic, noncholinergic relaxation in longitudinal muscle of the intestine of ICR mice. J Smooth Muscle Res. 1999; 35(3): 65-75[PubMed]
  • 25. D'Amato M, Curro D, Montuschi P, Ciabattoni G, Ragazzoni E, Lefebvre RA. Release of vasoactive intestinal polypeptide from the rat gastric fundus. Br J Pharmacol. 1992; 105(3): 691-5[PubMed]
  • 26. Radomirov R, Venkova K. Pharmacological characteristics of the postsynaptically mediated contractile responses of guinea-pig ileum to long-lasting electrical field stimulation. Neuropharmacology. 1988; 27(7): 729-35[PubMed]
  • 27. Ivancheva C, Pencheva N, Radomirov R. Pattern of nonadrenergic, noncholinergic responses during short- or long-lasting electrical stimulation in guinea-pig ileum. Gen Pharmacol. 1997; 29(2): 233-7[PubMed]
  • 28. Gozlan H, Thibault S, Laporte AM, Lima L, Hamon M. The selective 5-HT1A antagonist radioligand [3H]WAY 100635 labels both G-protein-coupled and free 5-HT1A receptors in rat brain membranes. Eur J Pharmacol. 1995; 288(2): 173-86[PubMed]
  • 29. Eglen RM, Jasper JR, Chang DJ, Martin GR. The 5-HT7 receptor: orphan found. Trends Pharmacol Sci. 1997; 18(4): 104-7[PubMed]
  • 30. Malleron JL, Comte MT, Gueremy C, Peyronel JF, Truchon A, Blanchard JC, et al. Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists. J Med Chem. 1991; 34(8): 2477-83[PubMed]
  • 31. Costa M, Furness JB. The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br J Pharmacol. 1979; 65(2): 237-48[PubMed]
  • 32. Engel G, Hoyer D, Kalkman HO, Wick MB. Identification of 5HT2-receptors on longitudinal muscle of the guinea pig ileum. J Recept Res. 1984; 4(1-6): 113-26[PubMed]
  • 33. Javid FA, Naylor RJ. Characterisation of 5-HT2 receptor subtypes in the Suncus murinus intestine. Eur J Pharmacol. 1999; 381(2-3): 161-9[PubMed]
  • 34. Leysen JE, Gommeren W, Van Gompel P, Wynants J, Janssen PF, Laduron PM. Receptor-binding properties in vitro and in vivo of ritanserin: A very potent and long acting serotonin-S2 antagonist. Mol Pharmacol. 1985; 27(6): 600-11[PubMed]
  • 35. Humphrey PP, Bountra C, Clayton N, Kozlowski K. Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 1999; 13 Suppl 2: 31-8[PubMed]
  • 36. Bianchi C, Beani L, Crema C. Effects of metoclopramide on isolated guinea-pig colon. 2. Interference with ganglionic stimulant drugs. Eur J Pharmacol. 1970; 12(3): 332-41[PubMed]
  • 37. Buchheit KH, Engel G, Mutschler E, Richardson B. Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum. Evidence for two distinct release mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1985; 329(1): 36-41[PubMed]
  • 38. Spencer NJ, Nicholas SJ, Sia TC, Staikopoulos V, Kyloh M, Beckett EA. By what mechanism does ondansetron inhibit colonic migrating motor complexes: does it require endogenous serotonin in the gut wall? Neurogastroenterol Motil. 2013; 25(8): 677-85[DOI][PubMed]
  • 39. Tan M. Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003; 4(9): 1563-71[DOI][PubMed]
  • 40. Hedge SS, Moy TM, Perry MR, Loeb M, Eglen RM. Evidence for the involvement of 5-hydroxytryptamine 4 receptors in 5-hydroxytryptophan-induced diarrhea in mice. J Pharmacol Exp Ther. 1994; 271(2): 741-7[PubMed]
  • 41. Budhoo MR, Harris RP, Kellum JM. The role of the 5-HT4 receptor in Cl- secretion in human jejunal mucosa. Eur J Pharmacol. 1996; 314(1-2): 109-14[PubMed]
  • 42. Kuemmerle JF, Murthy KS, Grider JR, Martin DC, Makhlouf GM. Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells. Gastroenterology. 1995; 109(6): 1791-800[PubMed]
  • 43. Yamamoto I, Kuwahara A, Fujimura M, Kadowaki M, Fujimiya M. Involvement of 5-HT3 and 5-HT4 receptors in the motor activity of isolated vascularly perfused rat duodenum. Neurogastroenterol Motil. 1999; 11(6): 457-65[PubMed]
  • 44. Gebauer A, Merger M, Kilbinger H. Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine. Naunyn Schmiedebergs Arch Pharmacol. 1993; 347(2): 137-40[PubMed]
  • 45. Irving HR, Tan YY, Tochon-Danguy N, Liu H, Chetty N, Desmond PV, et al. Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon. Life Sci. 2007; 80(13): 1198-205[DOI][PubMed]
  • 46. Tonini M, Vicini R, Cervio E, De Ponti F, De Giorgio R, Barbara G, et al. 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum. Gastroenterology. 2005; 129(5): 1557-66[DOI][PubMed]
  • 47. Carter D, Champney M, Hwang B, Eglen RM. Characterization of a postjunctional 5-HT receptor mediating relaxation of guinea-pig isolated ileum. Eur J Pharmacol. 1995; 280(3): 243-50[PubMed]
  • 48. Sia TC, Whiting M, Kyloh M, Nicholas SJ, Oliver J, Brookes SJ, et al. 5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT. Front Neurosci. 2013; 7: 136[DOI][PubMed]
  • 49. Keating DJ, Spencer NJ. Release of 5-hydroxytryptamine from the mucosa is not required for the generation or propagation of colonic migrating motor complexes. Gastroenterology. 2010; 138(2): 659-70 670 e1-2[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments