Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects
Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects
复制标题
DOI：
10.1152/ajpgi.90558.2008
复制
发表时间：
2009-02-01
影响因子：
4.5
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
--
作者：
Sweetser, Seth;Busciglio, Irene A.;Zinsmeister, Alan R.
Sweetser S，Busciglio IA，Camilleri M，Bharucha AE，Szarka LA，Papathanasopoulos A，Burton DD，Eckert DJ，Zinsmeister AR.氯离子通道激活剂鲁比前列酮对健康受试者结肠感觉和运动功能的影响。美国生理学杂志胃肠和肝脏生理学296：G295-G301，2009年。首次发表于2008年11月25日; doi：10.1152/ajpgi.90558.2008。鲁比前列酮是一种双环脂肪酸氯通道激活剂，可有效治疗慢性便秘和便秘型肠易激综合征。该研究的目的是比较鲁比前列酮和安慰剂对人类结肠感觉和运动功能的影响。在一项平行组、安慰剂对照试验中，以双盲、随机方式，60名健康成年人每天接受三次口服安慰剂或24 μ g鲁比前列酮。通过软式乙状结肠镜和荧光透视将恒压测压管放置在左结肠中。我们用经验证的方法测量了治疗对结肠感觉和运动的影响，终点如下：结肠顺应性、空腹和餐后张力和运动指数、疼痛阈值和对扩张的感觉评级。在接受鲁比前列酮或安慰剂的参与者中，分别有26/30和28/30完成了研究。鲁比前列酮对依从性、空腹张力、运动指数或感觉没有总体影响。然而，依从性存在治疗与性别的相互作用效应（P = 0.02），鲁比前列酮导致女性空腹依从性降低（P = 0.06），标准餐后结肠张力收缩相对于空腹张力总体降低（P = 0.014），女性的影响更大（P < 0.01）。两组的第一感觉和疼痛阈值（女性P = 0.11）的数值差异不显著。我们得出结论，口服鲁比前列酮24 μ g不会增加结肠运动功能。女性结肠顺应性降低和餐后结肠张力降低的结果表明，运动效应不太可能导致鲁比前列酮加速结肠运输，尽管它们可能促进排便。鲁比前列酮对敏感性的影响值得进一步研究。
Sweetser S, Busciglio IA, Camilleri M, Bharucha AE, Szarka LA, Papathanasopoulos A, Burton DD, Eckert DJ, Zinsmeister AR. Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. Am J Physiol Gastrointest Liver Physiol 296: G295-G301, 2009. First published November 25, 2008; doi:10.1152/ajpgi.90558.2008.-Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 mu g lubiprostone per day in a parallel-group, placebo-controlled trial. A barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy and fluoroscopy. We measured treatment effects on colonic sensation and motility with validated methods, with the following end points: colonic compliance, fasting and postprandial tone and motility indexes, pain thresholds, and sensory ratings to distensions. Among participants receiving lubiprostone or placebo, 26 of 30 and 28 of 30, respectively, completed the study. There were no overall effects of lubiprostone on compliance, fasting tone, motility indexes, or sensation. However, there was a treatment-by-sex interaction effect for compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in women (P = 0.06) and an overall decreased colonic tone contraction after a standard meal relative to fasting tone (P = 0.014), with greater effect in women (P < 0.01). Numerical differences of first sensation and pain thresholds (P = 0.11 in women) in the two groups were not significant. We concluded that oral lubiprostone 24 mu g does not increase colonic motor function. The findings of decreased colonic compliance and decreased postprandial colonic tone in women suggest that motor effects are unlikely to cause accelerated colonic transit with lubiprostone, although they may facilitate laxation. Effects of lubiprostone on sensitivity deserve further study.