Activation of peripheral 5-HT4 receptors attenuates colonic sensitivity to intraluminal distension

B. Greenwood-Van Meerveld, K. Venkova, G. Hicks, E. Dennis, M. D. Crowell

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Tegaserod is a 5-HT4 receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5-HT4 receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0-60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid-induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1-10 mg kg-1) caused dose-dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5-HT4 antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5-HT4 receptors.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalNeurogastroenterology and Motility
Volume18
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Receptors, Serotonin, 5-HT4
Hypersensitivity
Constipation
Abdominal Reflex
Colon
Serotonin 5-HT4 Receptor Antagonists
Trinitrobenzenesulfonic Acid
Intestinal Secretions
Peristalsis
Irritable Bowel Syndrome
Colitis
tegaserod
Acetic Acid
Pressure

Keywords

  • 5-HT receptors
  • Colorectal hypersensitivity
  • Rat
  • Tegaserod

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Activation of peripheral 5-HT4 receptors attenuates colonic sensitivity to intraluminal distension. / Greenwood-Van Meerveld, B.; Venkova, K.; Hicks, G.; Dennis, E.; Crowell, M. D.

In: Neurogastroenterology and Motility, Vol. 18, No. 1, 01.2006, p. 76-86.

Research output: Contribution to journalArticle

Greenwood-Van Meerveld, B. ; Venkova, K. ; Hicks, G. ; Dennis, E. ; Crowell, M. D. / Activation of peripheral 5-HT4 receptors attenuates colonic sensitivity to intraluminal distension. In: Neurogastroenterology and Motility. 2006 ; Vol. 18, No. 1. pp. 76-86.
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