The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin
The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin
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DOI：
10.1111/nmo.12259
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发表时间：
2014-02-01
影响因子：
3.5
通讯作者：
Furness, J. B.
中科院分区：
文献类型：
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作者：
Pustovit, R. V.;Callaghan, B.;Furness, J. B.
研究背景便秘的药物治疗一直是个难题.增加肠蠕动的数量被报道为一个副作用的乌立莫林治疗胃轻瘫，但一直没有调查的网站的action. MethodsAnesthesized大鼠被用来调查网站和机制的行动ulimorelin.Key ResultsIntravenous乌立莫林（1- 5毫克/公斤）引起了大量和长期（类似于1小时）增加结肠直肠推进活动和排出结肠内容物。通过切断腰骶髓神经、烟碱受体拮抗剂六甲双铵和生长激素释放肽受体拮抗剂可以防止这种情况。静脉注射乌立莫林的效果是模仿直接应用乌立莫林（5克）的腰骶spinalcord.Conclusions & InferencesUlimorelin是一种有效的prokinetic，通过激活胃饥饿素受体的腰骶排便中心，导致推进收缩的结肠直肠。它的效果是持久的，与其他靶向生长激素释放肽受体的coloketines相反。
BackgroundDiscovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action.MethodsAnesthetized rats were used to investigate sites and mechanisms of action of ulimorelin.Key ResultsIntravenous ulimorelin (1-5mg/kg) caused a substantial and prolonged (similar to 1h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5g) to the lumbosacral spinal cord.Conclusions & InferencesUlimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.