Bharucha A E, Camilleri M, Haydock S, Ferber I, Burton D, Cooper S, Tompson D, Fitzpatrick K, Higgins R, Zinsmeister A R
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Gut. 2000 Nov;47(5):667-74. doi: 10.1136/gut.47.5.667.
Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown.
Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist.
Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) 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 10-12 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.
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.
5-HT(4) 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.
5-羟色胺5-HT(4)受体位于肠胆碱能神经元上，可能调节蠕动。据推测，初级传入神经元上的5-HT(4)受体可调节内脏感觉。虽然5-HT(4)激动剂被用作促动力药物，但5-HT(4)受体在人体肠道中的生理作用尚不清楚。
我们的目的是通过使用5-HT(4)受体拮抗剂，来明确5-HT(4)受体在健康受试者基线和刺激条件下调节胃肠运动和感觉功能中的作用。
A部分比较了安慰剂与四剂5-HT(4)受体拮抗剂（SB-207266）对18名受试者中西沙必利介导的血浆醛固酮增加（一种5-HT(4)介导的反应）和口盲肠转运的影响。在B部分，52名健康受试者接受安慰剂，或0.05、0.5或5mg的SB-207266，持续10-12天；在第7-9天通过闪烁扫描测量胃、小肠和结肠转运，并在第12天评估空腹和餐后结肠运动功能、顺应性以及扩张期间的感觉。
A部分：0.5、5和20mg剂量的SB-207266具有显著且数量上相似的作用，拮抗西沙必利介导的血浆醛固酮增加和口盲肠转运加速。B部分：SB-207266倾向于延迟结肠转运（同位素在24小时（p=0.06）和48小时（p=0.08）的几何中心），但对转运、空腹或餐后结肠运动活动、顺应性或感觉没有剂量相关影响。
5-HT(4)受体参与西沙必利刺激的口盲肠转运调节；SB 207266倾向于调节健康人类受试者的结肠转运，但不影响感觉功能或顺应性。
