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Vol. 63, No. 3, 2001
Issue release date: 2001
Digestion 2001;63:188–194

Patients 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 Habits

Miwa J. · Echizen H. · Matsueda K. · Umeda N.
aDivision of Gastroenterology, International Medical Center of Japan, Tokyo, and bDepartment of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan

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Background: Serotonin (5-HT) may play an important role in the regulation of colonic motility in humans. However, it is not known whether alterations in the colonic 5-HT system are involved in the pathophysiology of irritable bowel syndrome (IBS). Methods: Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea- or constipation-predominant IBS (n = 7 and n = 8, respectively) and from subjects with normal bowel habits (n = 7) by endoscopic biopsy in order to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. The tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection. Results: In all study groups, the mean mucosal 5-HT concentrations obtained from the rectum were significantly (p < 0.05) higher than those obtained from more cephalic regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with constipation-predominant IBS were significantly (p < 0.05) higher than those obtained from the control subjects and patients with diarrhea-predominant IBS. No significant differences were observed in 5-hydroxyindoleacetic acid concentrations among the three groups. Conclusions: The mucosal 5-HT concentrations in the colon showed an ascending cephalocaudal gradient in all study groups. Although the mucosal 5-HT concentrations were elevated in patients with constipation-predominant IBS as compared with those with diarrhea-predominant IBS and the control subjects, further studies are necessary to determine whether the elevated mucosal 5-HT is a cause or a result of abnormal colonic motility.

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  1. Foxx-Orenstein AE, Kuemmerle JF, Grider JR: Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Gastroenterology 1996;111:1281–1290.
  2. Appel S, Kumle A, Meier R: Clinical pharmacodynamics of SDZ HTF919, a new 5-HT4 receptor agonist, in a model of slow colonic transit. Clin Pharmacol Ther 1997;62:546–555.
  3. Zimmerman TW, Binder HJ: Serotonin-induced alteration of colonic electrolyte transport in the rat. Gastroenterology 1984;86:310–317.

    External Resources

  4. Sidhu M, Cooke HJ: Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion. Am J Physiol 1995;269:G346–G351.

    External Resources

  5. von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM: Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea. N Engl J Med 1993;329:1073–1078.
  6. Grider JR, Kuemmerle JF, Jin JG: 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons. Am J Physiol 1996;270:G778–G782.

    External Resources

  7. Steadman CJ, Talley NJ, Phillips SF, Zinsmeister AR: Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: A pilot study. Mayo Clin Proc 1992;67:732–738.
  8. Prior A, Read NW: Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5-HT3 receptor antagonist, in patients with irritable bowel syndrome. Aliment Pharmacol Ther 1993;7:175–180.
  9. Talley NJ, Phillips SF, Haddad A, Miller LJ, Twomey C, Zinsmeister AR: GR38032F (ondansetron), a selective 5-HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci 1990;35:477–480.
  10. Gore S, Gilmore IT, Haigh CG, Brownless SM, Stockdale H, Morris AI: Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther 1990;4:139–144.
  11. Erspamer V, Asero B: Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature 1952;169:800–801.
  12. Lincoln J, Crowe R, Kamm MA, Burnstock G, Lennard-Jones JE: Serotonin and 5-hydroxyindoleacetic acid are increased in the sigmoidal colon in severe idiopathic constipation. Gastroenterology 1990;98:1219–1225.

    External Resources

  13. Drossman DA, Thompson GW, Talley NJ, Funch-Jensen P, Janssens J, Whitehead WE: Identification of subgroups of functional gastrointestinal disorders. Gastroenterol Int 1990;3:159–172.
  14. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.
  15. Koyama E, Minegishi A, Ishizaki T: Simultaneous determination of four monoamine metabolites and serotonin in cerebrospinal fluid by ‘high-perfomance’ liquid chromatography with electrochemical detection: Application for patients with Alzheimer’s disease. Clin Chem 1988;34:680–684.

    External Resources

  16. Kosterlitz HW, Lees GM: Pharmacological analysis of intrinsic intestinal reflexes. Pharmacol Rev 1964;16:301–339.
  17. Zhao R, Baig MK, Wexner SD, Chen W, Singh JJ, Nogueras JJ, Woodhouse S: Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia. Dis Colon Rectum 2000;43:858–863.
  18. El-Salhy M, Norrgard O, Spinnell S: Abnormal colonic endocrine cells in patients with chronic idiopathic slow-transit constipation. Scand J Gastroenterol 1999;34:1007–1011.
  19. Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD: Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 1996;16:2352–2364.

    External Resources

  20. Sanders-Bush E, Mayer SE: 5-Hydroxytryptamine (serotonin) receptor agonists and antagonists; in Hardman JG, Limbird LE, Molinoff PB, Ruddon R (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics, ed 9. New York, McGraw Hill, 1996, pp 249–263.
  21. Chugani DC, Muzik O, Chakraborty P, Mangner T, Chugani HT: Human brain serotonin synthesis capacity measured in vivo with alpha-[C11]methyl-L-tryptophan. Synapse 1998;28:33–43.
  22. Gill RC, Cote KR, Bowes KL, Kingma YJ: Human colonic smooth muscle: Spontaneous contractile activity and response to stretch. Gut 1986;27:1006–1013.

    External Resources

  23. Fink S, Freedman G: The differential effects of drugs on the proximal and distal colon. Am J Med 1960;28:534–540.
  24. Lembo T, Naliboff B, Munakata J, Fullerton S, Saba L, Tung S, Schmulson M, Mayer EA: Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroenterol 1999;94:1320–1326.
  25. Schmulson M, Chang L, Naliboff B, Lee OY, Meyer EA: Correlation of symptom criteria with perception thresholds during rectosigmoid distension in irritable bowel syndrome patients. Am J Gastroenterol 2000;95:152–156.

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