Diseases of the Colon & Rectum

, Volume 50, Issue 3, pp 376–388 | Cite as

Serotonin and Its Role in Colonic Function and in Gastrointestinal Disorders

  • Meagan M. Costedio
  • Neil Hyman
  • Gary M. MaweEmail author
Current Status

Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central nervous system. However, the predominant site of serotonin synthesis, storage, and release is the enterochromaffin cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility, and sensation. Two important receptors for serotonin that are located in the neural circuitry of the intestines are the 5-HT3 and 5-HT4 receptors; these are the targets of drugs designed to treat gastrointestinal disorders. 5-HT3 receptor antagonists are used to treat nausea and emesis associated with chemotherapy and for functional disorders associated with diarrhea. 5-HT4 receptor agonists are used as promotility agents to promote gastric emptying and to alleviate constipation. Because of the importance of serotonin in normal gut function and sensation, a number of studies have investigated potential changes in mucosal serotonin signaling in pathologic conditions. Despite the inconsistencies in the current literature, changes in serotonin signaling have now been demonstrated in inflammatory bowel disease, irritable bowel syndrome, postinfectious irritable bowel syndrome, and idiopathic constipation. Emerging evidence has led to many contradictory theories regarding serotonin signaling and its roles in the pathology of gut disorders. This review summarizes the current medications affecting serotonin signaling and provides an overview of our current knowledge of the changes in serotonin that occur in pathologic conditions.

Key words

Irritable bowel syndrome Constipation Enterochromaffin cells 5-HT3 and 5-HT4 receptors 



The authors thank Michael J. Callahan Ph.D. for valuable input during the preparation of this review.


  1. 1.
    Bayliss, WM, Starling, EH 1899The movements and innervation of the small intestineJ Physiol2499143PubMedGoogle Scholar
  2. 2.
    Bayliss, WM, Starling, EH 1900The movements and innervation of the small intestineJ Physiol26107138PubMedGoogle Scholar
  3. 3.
    Bulbring, E, Crema, A 1959The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosaJ Physiol1461828PubMedGoogle Scholar
  4. 4.
    Erspamer, V, Vialli, M 1937Ricerche sul secreto delle cellule enterochromaffiniBoll Soc Med Chir Pavia51357363Google Scholar
  5. 5.
    Whitaker-Azmitia, PM 1999The discovery of serotonin and its role in neuroscienceNeuropsychopharmacology212S8SPubMedGoogle Scholar
  6. 6.
    Page, IH 1952The vascular action of natural serotonin, 5- and 7-hydroxytryptamine and tryptamineJ Pharmacol Exp Ther1055873PubMedGoogle Scholar
  7. 7.
    Page, IH 1954Serotonin (5-hydroxytryptamine)Physiol Rev34563588PubMedGoogle Scholar
  8. 8.
    Bulbring, E, Crema, A 1959The action of 5-hydroxytryptamine, 5-hydroxytryptophan and reserpine on intestinal peristalsis in anaesthetized guinea-pigsJ Physiol1462953PubMedGoogle Scholar
  9. 9.
    Bulbring, E, Lin, RC 1958The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activityJ Physiol140381407PubMedGoogle Scholar
  10. 10.
    Racke, K, Reimann, A, Schworer, H, Kilbinger, H 1996Regulation of 5-HT release from enterochromaffin cellsBehav Brain Res738387PubMedGoogle Scholar
  11. 11.
    Racke, K, Schworer, H 1991Regulation of serotonin release from the intestinal mucosaPharmacol Res231325PubMedGoogle Scholar
  12. 12.
    Gaddum, JH, Picarelli, ZP 1957Two kinds of tryptamine receptorBr J Pharmacol Chemother12323328PubMedGoogle Scholar
  13. 13.
    Gershon, MD 1968Serotonin and the motility of the gastrointestinal tractGastroenterology54453456PubMedGoogle Scholar
  14. 14.
    Kim, DY, Camilleri, M 2000Serotonin: A mediator of the brain-gut connectionAm J Gastroenterol9526982709PubMedGoogle Scholar
  15. 15.
    Gershon, RR, Vlahov, D, Kelen, G, Conrad, B, Murphy, L 1995Review of accidents/injuries among emergency medical services workers in Baltimore, MarylandPrehospital Disaster Med101418PubMedGoogle Scholar
  16. 16.
    Gershon, MD 2004Review article: Serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motilityAliment Pharmacol Ther20314PubMedGoogle Scholar
  17. 17.
    Crowell, MD, Shetzline, MA, Moses, PL, Mawe, GM, Talley, NJ 2004Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal functionCurr Opin Investig Drugs55560PubMedGoogle Scholar
  18. 18.
    Goyal, RK, Hirano, I 1996The enteric nervous systemN Engl J Med33411061115PubMedGoogle Scholar
  19. 19.
    Bulbring, E, Gershon, MD 19675-hydroxytryptamine participation in the vagal inhibitory innervation of the stomachJ Physiol192823846PubMedGoogle Scholar
  20. 20.
    Grundy, D 2002Towards a reduction of rectal pain?Neurogastroenterol Motil14217219PubMedGoogle Scholar
  21. 21.
    Kirkup, AJ, Brunsden, AM, Grundy, D 2001Receptors and transmission in the brain-gut axis: Potential for novel therapies. I. Receptors on visceral afferentsAm J Physiol Gastrointest Liver Physiol280G787G794PubMedGoogle Scholar
  22. 22.
    Fuller, RW, Wong, DT 1990Serotonin uptake and serotonin uptake inhibitionAnn N Y Acad Sci6006880PubMedGoogle Scholar
  23. 23.
    Prada, M, Tranzer, JP, Pletscher, A 1972Storage of 5-hydroxytryptamine in human blood plateletsExperientia2813281329PubMedGoogle Scholar
  24. 24.
    Gershon, MD 1991Serotonin: Its role and receptors in enteric neurotransmissionAdv Exp Med Biol294221230PubMedGoogle Scholar
  25. 25.
    Wallis, DI, Stansfeld, CE, Nash, HL 1982Depolarizing responses recorded from nodose ganglion cells of the rabbit evoked by 5-hydroxytryptamine and other substancesNeuropharmacology213140PubMedGoogle Scholar
  26. 26.
    Cash, BD, Chey, WD 2005Review article: The role of serotonergic agents in the treatment of patients with primary chronic constipationAliment Pharmacol Ther2210471060PubMedGoogle Scholar
  27. 27.
    Hargreaves, AC, Lummis, SC, Taylor, CW 1994Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptorsMol Pharmacol4611201128PubMedGoogle Scholar
  28. 28.
    Camilleri, M 2004Treating irritable bowel syndrome: Overview, perspective and future therapiesBr J Pharmacol14112371248PubMedGoogle Scholar
  29. 29.
    Cremonini, F, Delgado-Aros, S, Camilleri, M 2003Efficacy of alosetron in irritable bowel syndrome: A meta-analysis of randomized controlled trialsNeurogastroenterol Motil157986PubMedGoogle Scholar
  30. 30.
    Delvaux, M, Louvel, D, Mamet, JP, Campos-Oriola, R, Frexinos, J 1998Effect of alosetron on responses to colonic distension in patients with irritable bowel syndromeAliment Pharmacol Ther12849855PubMedGoogle Scholar
  31. 31.
    Jones, RH, Holtmann, G, Rodrigo, L,  et al. 1999Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patientsAliment Pharmacol Ther1314191427PubMedGoogle Scholar
  32. 32.
    Lembo, T, Wright, RA, Bagby, B,  et al. 2001Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndromeAm J Gastroenterol9626622670PubMedGoogle Scholar
  33. 33.
    Olden, KW, Crowell, MD 2005CilansetronDrugs Today (Barc)41661666Google Scholar
  34. 34.
    Brandt, LJ, Prather, CM, Quigley, EM, Schiller, LR, Schoenfeld, P, Talley, NJ 2005Systematic review on the management of chronic constipation in north americaAm J Gastroenterol100S5S21PubMedGoogle Scholar
  35. 35.
    Callahan, MJ 2002Irritable bowel syndrome neuropharmacology. A review of approved and investigational compoundsJ Clin Gastroenterol35S58S67PubMedGoogle Scholar
  36. 36.
    Camilleri, M 2001Review article: TegaserodAliment Pharmacol Ther15277289PubMedGoogle Scholar
  37. 37.
    Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2004; CD003960Google Scholar
  38. 38.
    Kamm, MA, Muller-Lissner, S, Talley, NJ,  et al. 2005Tegaserod for the treatment of chronic constipation: A randomized, double-blind, placebo-controlled multinational studyAm J Gastroenterol100362372PubMedGoogle Scholar
  39. 39.
    Muller-Lissner, SA, Fumagalli, I, Bardhan, KD,  et al. 2001Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipationAliment Pharmacol Ther1516551666PubMedGoogle Scholar
  40. 40.
    Nyhlin, H, Bang, C, Elsborg, L,  et al. 2004A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndromeScand J Gastroenterol39119126PubMedGoogle Scholar
  41. 41.
    Jailwala, J, Imperiale, TF, Kroenke, K 2000Pharmacologic treatment of the irritable bowel syndrome: A systematic review of randomized, controlled trialsAnn Intern Med133136147PubMedGoogle Scholar
  42. 42.
    Kamm, MA 2002Review article: The complexity of drug development for irritable bowel syndromeAliment Pharmacol Ther16343351PubMedGoogle Scholar
  43. 43.
    Ziegenhagen, DJ, Kruis, W 2004Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placeboJ Gastroenterol Hepatol19744749PubMedGoogle Scholar
  44. 44.
    Bouras, EP, Camilleri, M, Burton, DD, Thomforde, G, McKinzie, S, Zinsmeister, AR 2001Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorderGastroenterology120354360PubMedGoogle Scholar
  45. 45.
    Coremans, G, Kerstens, R, Pauw, M, Stevens, M 2003Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trialDigestion678289PubMedGoogle Scholar
  46. 46.
    Schryver, AM, Andriesse, GI, Samsom, M, Smout, AJ, Gooszen, HG, Akkermans, LM 2002The effects of the specific 5HT(4) receptor agonist, prucalopride, on colonic motility in healthy volunteersAliment Pharmacol Ther16603612PubMedGoogle Scholar
  47. 47.
    Emmanuel, AV, Roy, AJ, Nicholls, TJ, Kamm, MA 2002Prucalopride, a systemic enterokinetic, for the treatment of constipationAliment Pharmacol Ther1613471356PubMedGoogle Scholar
  48. 48.
    Sloots, CE, Poen, AC, Kerstens, R,  et al. 2002Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipationAliment Pharmacol Ther16759767PubMedGoogle Scholar
  49. 49.
    Bharucha, AE, Camilleri, M, Haydock, S,  et al. 2000Effects of a serotonin 5-HT(4) receptor antagonist sb-207266 on gastrointestinal motor and sensory function in humansGut47667674PubMedGoogle Scholar
  50. 50.
    Houghton, LA, Jackson, NA, Whorwell, PJ, Cooper, SM 19995-HT4 receptor antagonism in irritable bowel syndrome: Effect of sb-207266-a on rectal sensitivity and small bowel transitAliment Pharmacol Ther1314371444PubMedGoogle Scholar
  51. 51.
    Sanger, GJ, Banner, SE, Smith, MI, Wardle, KA 1998Sb-207266: 5-HT4 receptor antagonism in human isolated gut and prevention of 5-HT-evoked sensitization of peristalsis and increased defaecation in animal modelsNeurogastroenterol Motil10271279PubMedGoogle Scholar
  52. 52.
    Tonini, M, Ponti, F, Nucci, A, Crema, F 1999Review article: Cardiac adverse effects of gastrointestinal prokineticsAliment Pharmacol Ther1315851591PubMedGoogle Scholar
  53. 53.
    Camilleri, M, McKinzie, S, Fox, J,  et al. 2004Effect of renzapride on transit in constipation-predominant irritable bowel syndromeClin Gastroenterol Hepatol2895904PubMedGoogle Scholar
  54. 54.
    Galligan, JJ, Vanner, S 2005Basic and clinical pharmacology of new motility promoting agentsNeurogastroenterol Motil17643653PubMedGoogle Scholar
  55. 55.
    Potet, F, Bouyssou, T, Escande, D, Baro, I 2001Gastrointestinal prokinetic drugs have different affinity for the human cardiac human ether-a-gogo k(+) channelJ Pharmacol Exp Ther29910071012PubMedGoogle Scholar
  56. 56.
    Carlsson, L, Amos, GJ, Andersson, B, Drews, L, Duker, G, Wadstedt, G 1997Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: Implications for proarrhythmic potential?J Pharmacol Exp Ther282220227PubMedGoogle Scholar
  57. 57.
    Mine, Y, Yoshikawa, T, Oku, S, Nagai, R, Yoshida, N, Hosoki, K 1997Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro J Pharmacol Exp Ther28310001008PubMedGoogle Scholar
  58. 58.
    Bertrand, PP, Kunze, WA, Furness, JB, Bornstein, JC 2000The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptorsNeuroscience101459469PubMedGoogle Scholar
  59. 59.
    Galligan, JJ 1996Electrophysiological studies of 5-hydroxytryptamine receptors on enteric neuronsBehav Brain Res73199201PubMedGoogle Scholar
  60. 60.
    Galligan, JJ 2002Pharmacology of synaptic transmission in the enteric nervous systemCurr Opin Pharmacol2623629PubMedGoogle Scholar
  61. 61.
    Costall, B, Naylor, RJ 20045-HT3 receptorsCurr Drug Targets CNS Neurol Disord32737PubMedGoogle Scholar
  62. 62.
    Talley, NJ, Phillips, SF, Haddad, A,  et al. 1990Gr 38032f (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy manDig Dis Sci35477480PubMedGoogle Scholar
  63. 63.
    Ohe, MR, Hanson, RB, Camilleri, M 1994Serotonergic mediation of postprandial colonic tonic and phasic responses in humansGut35536541PubMedGoogle Scholar
  64. 64.
    Camilleri, M, Chey, WY, Mayer, EA,  et al. 2001A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndromeArch Intern Med16117331740PubMedGoogle Scholar
  65. 65.
    Camilleri, M, Northcutt, AR, Kong, S, Dukes, GE, McSorley, D, Mangel, AW 2000Efficacy and safety of alosetron in women with irritable bowel syndrome: A randomised, placebo-controlled trialLancet35510351040PubMedGoogle Scholar
  66. 66.
    Bockaert, J, Claeysen, S, Compan, V, Dumuis, A 20045-HT4 receptorsCurr Drug Targets CNS Neurol Disord33951PubMedGoogle Scholar
  67. 67.
    Foxx-Orenstein, AE, Jin, JG, Grider, JR 19985-HT4 receptor agonists and delta-opioid receptor antagonists act synergistically to stimulate colonic propulsionAm J Physiol275G979G983PubMedGoogle Scholar
  68. 68.
    Liu, M, Geddis, MS, Wen, Y, Setlik, W, Gershon, MD 2005Expression and function of 5-HT4 receptors in the mouse enteric nervous systemAm J Physiol Gastrointest Liver Physiol289G1148G1163PubMedGoogle Scholar
  69. 69.
    Grider, JR 2006Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserodAm J Physiol Gastrointest Liver Physiol290G319G327PubMedGoogle Scholar
  70. 70.
    Galligan, JJ, Pan, H, Messori, E 2003Signalling mechanism coupled to 5-hydroxytryptamine4 receptor-mediated facilitation of fast synaptic transmission in the guinea-pig ileum myenteric plexusNeurogastroenterol Motil15523529PubMedGoogle Scholar
  71. 71.
    Pan, H, Galligan, JJ 19945-HT1a and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neuronsAm J Physiol266G230G238PubMedGoogle Scholar
  72. 72.
    Grider, JR, Foxx-Orenstein, AE, Jin, JG 19985-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestineGastroenterology115370380PubMedGoogle Scholar
  73. 73.
    Jin, JG, Foxx-Orenstein, AE, Grider, JR 1999Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptorsJ Pharmacol Exp Ther2889397PubMedGoogle Scholar
  74. 74.
    Lyford, G, Foxx-Orenstein, A 2004Chronic intestinal pseudoobstructionCurr Treat Options Gastroenterol7317325PubMedGoogle Scholar
  75. 75.
    Ferriman, A 2000UK licence for cisapride suspendedBMJ321259PubMedGoogle Scholar
  76. 76.
    Linden, DR, Chen, JX, Gershon, MD, Sharkey, KA, Mawe, GM 2003Serotonin availability is increased in mucosa of guinea pigs with tnbs-induced colitisAm J Physiol Gastrointest Liver Physiol285G207G216PubMedGoogle Scholar
  77. 77.
    O’Hara, JR, Ho, W, Linden, DR, Mawe, GM, Sharkey, KA 2004Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitisAm J Physiol Gastrointest Liver Physiol287G998G1007PubMedGoogle Scholar
  78. 78.
    Linden, DR, Foley, KF, McQuoid, C, Simpson, J, Sharkey, KA, Mawe, GM 2005Serotonin transporter function and expression are reduced in mice with TNBS-induced colitisNeurogastroenterol Motil1756574PubMedGoogle Scholar
  79. 79.
    Wheatcroft, J, Wakelin, D, Smith, A, Mahoney, CR, Mawe, G, Spiller, R 2005Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunctionNeurogastroenterol Motil17863870PubMedGoogle Scholar
  80. 80.
    O’Hara, JR, Skinn, AC, MacNaughton, WK, Sherman, PM, Sharkey, KA 2006Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colonCell Microbiol8646660PubMedGoogle Scholar
  81. 81.
    Coates, MD, Mahoney, CR, Linden, DR,  et al. 2004Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndromeGastroenterology12616571664PubMedGoogle Scholar
  82. 82.
    Ahonen, A, Kyosola, K, Penttila, O 1976Enterochromaffin cells in macrophages in ulcerative colitis and irritable colonAnn Clin Res817PubMedGoogle Scholar
  83. 83.
    Magro, F, Vieira-Coelho, MA, Fraga, S,  et al. 2002Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel diseaseDig Dis Sci47216224PubMedGoogle Scholar
  84. 84.
    El-Salhy, M, Danielsson, A, Stenling, R, Grimelius, L 1997Colonic endocrine cells in inflammatory bowel diseaseJ Intern Med242413419PubMedGoogle Scholar
  85. 85.
    Bearcroft, CP, Perrett, D, Farthing, MJ 1998Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: A pilot studyGut424246PubMedCrossRefGoogle Scholar
  86. 86.
    Miwa, J, Echizen, H, Matsueda, K, Umeda, N 2001Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habitsDigestion63188194PubMedGoogle Scholar
  87. 87.
    Atkinson, W, Lockhart, S, Whorwell, PJ, Keevil, B, Houghton, LA 2006Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndromeGastroenterology1303443PubMedGoogle Scholar
  88. 88.
    Dunlop, SP, Coleman, NS, Blackshaw, E,  et al. 2005Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndromeClin Gastroenterol Hepatol3349357PubMedGoogle Scholar
  89. 89.
    Spiller, RC, Jenkins, D, Thornley, JP,  et al. 2000Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndromeGut47804811PubMedGoogle Scholar
  90. 90.
    Dunlop, SP, Jenkins, D, Neal, KR, Spiller, RC 2003Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBSGastroenterology12516511659PubMedGoogle Scholar
  91. 91.
    Lincoln, J, Crowe, R, Kamm, MA, Burnstock, G, Lennard-Jones, JE 1990Serotonin and 5-hydroxyindoleacetic acid are increased in the sigmoid colon in severe idiopathic constipationGastroenterology9812191225PubMedGoogle Scholar
  92. 92.
    Zhao, R, Baig, MK, Wexner, SD,  et al. 2000Enterochromaffin and serotonin cells are abnormal for patients with colonic inertiaDis Colon Rectum43858863PubMedGoogle Scholar
  93. 93.
    Simren, M, Axelsson, J, Gillberg, R, Abrahamsson, H, Svedlund, J, Bjornsson, ES 2002Quality of life in inflammatory bowel disease in remission: The impact of IBS-like symptoms and associated psychological factorsAm J Gastroenterol97389396PubMedGoogle Scholar
  94. 94.
    Neal, KR, Hebden, J, Spiller, R 1997Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: Postal survey of patientsBMJ314779782PubMedGoogle Scholar
  95. 95.
    Drossman, DA, Whitehead, WE, Camilleri, M 1997Irritable bowel syndrome: A technical review for practice guideline developmentGastroenterology11221202137PubMedGoogle Scholar
  96. 96.
    Chadwick, VS, Chen, W, Shu, D,  et al. 2002Activation of the mucosal immune system in irritable bowel syndromeGastroenterology12217781783PubMedGoogle Scholar
  97. 97.
    Tornblom, H, Lindberg, G, Nyberg, B, Veress, B 2002Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndromeGastroenterology12319721979PubMedGoogle Scholar
  98. 98.
    Mertz, H, Morgan, V, Tanner, G,  et al. 2000Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distentionGastroenterology118842848PubMedGoogle Scholar
  99. 99.
    Locke, GR,3rd, Zinsmeister, AR, Talley, NJ, Fett, SL, Melton, LJ,3rd 2000Familial association in adults with functional gastrointestinal disordersMayo Clin Proc75907912PubMedCrossRefGoogle Scholar
  100. 100.
    Nobaek, S, Johansson, ML, Molin, G, Ahrne, S, Jeppsson, B 2000Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndromeAm J Gastroenterol9512311238PubMedGoogle Scholar
  101. 101.
    Gershon, MD 2005Nerves, reflexes, and the enteric nervous system: Pathogenesis of the irritable bowel syndromeJ Clin Gastroenterol39S184S193PubMedGoogle Scholar
  102. 102.
    Chen, JJ, Li, Z, Pan, H,  et al. 2001Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transportersJ Neurosci2163486361PubMedGoogle Scholar
  103. 103.
    Coates, MD, Johnson, AC, Greenwood-Van Meerveld, B, Mawe, GM 2006Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouseNeurogastroenterol Motil18464471PubMedGoogle Scholar
  104. 104.
    Camilleri, M, Mayer, EA, Drossman, DA,  et al. 1999Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonistAliment Pharmacol Ther1311491159PubMedGoogle Scholar
  105. 105.
    Ponti, F, Tonini, M 2001Irritable bowel syndrome: New agents targeting serotonin receptor subtypesDrugs61317332PubMedGoogle Scholar
  106. 106.
    Knowles, CH, Scott, M, Lunniss, PJ 1999Outcome of colectomy for slow transit constipationAnn Surg230627638PubMedGoogle Scholar
  107. 107.
    Sonnenberg, A, Koch, TR 1989Epidemiology of constipation in the United StatesDis Colon Rectum3218PubMedGoogle Scholar
  108. 108.
    Voderholzer, WA, Schatke, W, Muhldorfer, BE, Klauser, AG, Birkner, B, Muller-Lissner, SA 1997Clinical response to dietary fiber treatment of chronic constipationAm J Gastroenterol929598PubMedGoogle Scholar
  109. 109.
    He, CL, Burgart, L, Wang, L,  et al. 2000Decreased interstitial cell of Cajal volume in patients with slow-transit constipationGastroenterology1181421PubMedGoogle Scholar
  110. 110.
    Tong, WD, Liu, BH, Zhang, LY, Zhang, SB, Lei, Y 2004Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipationInt J Colorectal Dis19467473PubMedGoogle Scholar
  111. 111.
    Facer, P, Knowles, CH, Thomas, PK, Tam, PK, Williams, NS, Anand, P 2001Decreased tyrosine kinase C expression may reflect developmental abnormalities in Hirschsprung’s disease and idiopathic slow-transit constipationBr J Surg88545552PubMedGoogle Scholar
  112. 112.
    Knowles, CH, Gayther, SA, Scott, M,  et al. 2000Idiopathic slow-transit constipation is not associated with mutations of the ret proto-oncogene or GDNFDis Colon Rectum43851857PubMedGoogle Scholar
  113. 113.
    Altomare, DF, Portincasa, P, Rinaldi, M,  et al. 1999Slow-transit constipation: Solitary symptom of a systemic gastrointestinal diseaseDis Colon Rectum42231240PubMedGoogle Scholar
  114. 114.
    Xiao, ZL, Pricolo, V, Biancani, P, Behar, J 2005Role of progesterone signaling in the regulation of g-protein levels in female chronic constipationGastroenterology128667675PubMedGoogle Scholar
  115. 115.
    Bueno, L, Fioramonti, J 1988Action of opiates on gastrointestinal functionBaillieres Clin Gastroenterol2123139PubMedGoogle Scholar
  116. 116.
    Fotherby, KJ, Hunter, JO 1987Idiopathic slow-transit constipation: Whole gut transit times, measured by a new simplified method, are not shortened by opioid antagonistsAliment Pharmacol Ther1331338PubMedCrossRefGoogle Scholar
  117. 117.
    Sonsino, E, Mouy, R, Foucaud, P,  et al. 1984Intestinal pseudo-obstruction related to cytomegalovirus infection of myenteric plexusN Engl J Med311196197PubMedGoogle Scholar
  118. 118.
    Sykes, NP 1991Oral naloxone in opioid-associated constipationLancet3371475PubMedGoogle Scholar
  119. 119.
    Vassallo, M, Camilleri, M, Caron, BL, Low, PA 1991Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosisGastroenterology100252258PubMedGoogle Scholar
  120. 120.
    Knowles, CH, Martin, JE 2000Slow transit constipation: A model of human gut dysmotility. Review of possible aetiologiesNeurogastroenterol Motil12181196PubMedGoogle Scholar
  121. 121.
    Zhao, RH, Baig, MK, Thaler, KJ,  et al. 2003Reduced expression of serotonin receptor(s) in the left colon of patients with colonic inertiaDis Colon Rectum468186PubMedGoogle Scholar
  122. 122.
    Johanson, JF, Wald, A, Tougas, G,  et al. 2004Effect of tegaserod in chronic constipation: A randomized, double-blind, controlled trialClin Gastroenterol Hepatol2796805PubMedGoogle Scholar
  123. 123.
    Piccirillo, MF, Reissman, P, Wexner, SD 1995Colectomy as treatment for constipation in selected patientsBr J Surg82898901PubMedGoogle Scholar
  124. 124.
    FitzHarris, GP, Garcia-Aguilar, J, Parker, SC,  et al. 2003Quality of life after subtotal colectomy for slow-transit constipation: Both quality and quantity countDis Colon Rectum46433440PubMedGoogle Scholar
  125. 125.
    Saunders, MD, Kimmey, MB 2005Systematic review: Acute colonic pseudo-obstructionAliment Pharmacol Ther22917925PubMedGoogle Scholar
  126. 126.
    Giorgio, R, Barbara, G, Stanghellini, V,  et al. 2001Review article: The pharmacological treatment of acute colonic pseudo-obstructionAliment Pharmacol Ther1517171727PubMedGoogle Scholar
  127. 127.
    Paran, H, Silverberg, D, Mayo, A, Shwartz, I, Neufeld, D, Freund, U 2000Treatment of acute colonic pseudo-obstruction with neostigmineJ Am Coll Surg190315318PubMedGoogle Scholar
  128. 128.
    Ponec, RJ, Saunders, MD, Kimmey, MB 1999Neostigmine for the treatment of acute colonic pseudo-obstructionN Engl J Med341137141PubMedGoogle Scholar
  129. 129.
    Stephenson, BM, Morgan, AR, Salaman, JR, Wheeler, MH 1995Ogilvie’s syndrome: A new approach to an old problemDis Colon Rectum38424427PubMedGoogle Scholar
  130. 130.
    Trevisani, GT, Hyman, NH, Church, JM 2000Neostigmine: Safe and effective treatment for acute colonic pseudo-obstructionDis Colon Rectum43599603PubMedGoogle Scholar
  131. 131.
    MacColl, C, MacCannell, KL, Baylis, B, Lee, SS 1990Treatment of acute colonic pseudo-obstruction (Ogilvie’s syndrome) with cisaprideGastroenterology98773776PubMedGoogle Scholar
  132. 132.
    Pelckmans, PA, Michielsen, PP, Jorens, PG, Maercke, YM 1990Cisapride in Ogilvie’s syndromeGastroenterology9911945PubMedGoogle Scholar

Copyright information

© The American Society of Colon and Rectal Surgeons 2007

Authors and Affiliations

  • Meagan M. Costedio
    • 1
  • Neil Hyman
    • 1
  • Gary M. Mawe
    • 2
    Email author
  1. 1.Department of SurgeryUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of Anatomy and NeurobiologyUniversity of Vermont College of MedicineBurlingtonUSA

Personalised recommendations