TY - JOUR
T1 - Effects of a serotonin 5-HT4 receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans
AU - Bharucha, A. E.
AU - Zinsmeister, A. R.
AU - Camilleri, M.
AU - Haydock, S.
AU - Ferber, I.
AU - Burton, D.
AU - Cooper, S.
AU - Tompson, D.
AU - Fitzpatrick, K.
AU - Higgins, R.
PY - 2000
Y1 - 2000
N2 - Background - Serotonin 5-HT4 receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT4 receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT4 agonists are used as prokinetic agents, the physiological role of 5-HT4 receptors in the human gut is unknown. Aims - Our aim was to characterise the role of 5-HT4 receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT4 receptor antagonist. Methods - Part A compared the effects of placebo to four doses of a 5-HT4 receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT4 mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 16-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. Results - Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. Conclusion - 5-HT4 receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.
AB - Background - Serotonin 5-HT4 receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT4 receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT4 agonists are used as prokinetic agents, the physiological role of 5-HT4 receptors in the human gut is unknown. Aims - Our aim was to characterise the role of 5-HT4 receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT4 receptor antagonist. Methods - Part A compared the effects of placebo to four doses of a 5-HT4 receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT4 mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 16-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. Results - Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. Conclusion - 5-HT4 receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.
KW - 5-HT
KW - Colon transit
KW - Gastrointestinal motor function
KW - Gastrointestinal sensory function
KW - Receptors
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U2 - 10.1136/gut.47.5.667
DO - 10.1136/gut.47.5.667
M3 - Article
C2 - 11034583
AN - SCOPUS:0033755876
SN - 0017-5749
VL - 47
SP - 667
EP - 674
JO - Gut
JF - Gut
IS - 5
ER -