Modulation of intestinal gas dynamics in healthy human volunteers by the 5-HT receptor agonist tegaserod.
Modulation of intestinal gas dynamics in healthy human volunteers by the 5-HT receptor agonist tegaserod.
复制标题
5-HT 受体激动剂替加色罗对健康志愿者肠道气体动力学的调节。
DOI：
10.1111/j.1572-0241.2006.00708.x
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Hasler,WilliamL
中科院分区：
文献类型：
--
作者：
Coleski,Radoslav;Owyang,Chung;Hasler,WilliamL
OBJECTIVESBloating in irritable bowel syndrome (IBS) may result from impaired intestinal gas transit and is reduced by the 5-HT 4 agonist tegaserod. Abnormal serotonergic function underlies many IBS symptoms, but the role of 5-HT 4 pathways in regulating gas dynamics under healthy conditions is unexplored. We hypothesized that 5-HT 4 activation by tegaserod stimulates gas transit in healthy individuals.METHODSSixteen normal volunteers underwent jejunal perfusion of gas mixtures (88% N 2, 5.5% O 2, 6.5% CO 2) at 11.2 mL/min× 3 h under control conditions and 3 h after oral tegaserod 6 mg on separate days. Gas collected from an intrarectal catheter was quantified using a barostat.RESULTSUnder control conditions, gas evacuation after a lag period (1,959±428 s) was predominantly pulsatile with expulsion of 1,984±90 mL. A mean of 29±2 boluses with volumes of 72±5 mL were expelled. In 10 subjects with physiologic degrees of gas retention in control studies (248±73 mL), tegaserod increased expulsion from 1,768±73 to 1,973±37 mL and decreased retention to 43±37 mL (p< 0.05). Total volumes expelled as boluses were greater after tegaserod (1,708±73 vs 1,846±59 mL, p< 0.05) from increased bolus numbers in four subjects and increased bolus volumes in seven. Nonpulsatile continuous flow tended to increase with tegaserod (43±7 vs 126±43 mL, p= 0.10). Tegaserod did not increase evacuation in individuals without physiologic gas retention.CONCLUSIONSThe 5-HT 4 agonist tegaserod promotes evacuation of jejunally perfused gas mixtures in healthy humans. These findings provide the foundation for future investigations into use of 5-HT 4 agonists in conditions of pathologic gas retention.
