Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors.
Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors.
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发表时间：
1999
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通讯作者：
J. Jin;A. Foxx-Orenstein;J. Grider
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作者：
J. Jin;A. Foxx-Orenstein;J. Grider
以往的研究表明，肠蠕动反射是由肠嗜铬细胞释放5-羟色胺（HT）介导的，在大鼠和人中，5-HT通过5-HT 4受体起作用，在豚鼠中，5-HT 4和5-HT 3受体共同激活肠壁感觉神经元，释放降钙素基因相关肽。在这项研究中，选择性激动剂和拮抗剂被用来检查参与5-HT 4和5-HT 3受体在结肠推进。在离体豚鼠结肠段口端注入人工粪粒，测定其推进速度。控制速度范围为0.5 - 3.3 mm/s;平均值+/- S.E.M.，1.3± 0.1 mm/s。5-HT 4拮抗剂GR 113808 A和5-HT 3拮抗剂LY 278584以浓度依赖性方式降低颗粒推进速度（在10 μ M时分别降低39 +/- 2%和47 +/- 1%）。两种拮抗剂（各10 μ M）的组合是相加的，使速度降低82 +/- 3%至84 +/-4%。选择性5-HT 4激动剂HTF 919和R 093877以及5-HT在5-HT 2a拮抗剂酮色林存在下以浓度依赖性方式增加推进速度，EC 50分别为6.9 +/- 0.1 nM、37.4 +/- 1.0 nM和3.9 +/- 0.1 nM。1 nM。与HTF 919相比，R 093877的效力较低，似乎是一种部分激动剂。所有三种激动剂在亚微摩尔浓度下都有效;在1微摩尔浓度以上，推进速度没有增加。我们的结论是粪便颗粒的存在触发5-HT的释放，其通过5-HT 3和5-HT 4受体来调节豚鼠结肠的推进活动。
Previous studies have shown that the intestinal peristaltic reflex initiated by mucosal stimulation is mediated by release of 5-hydroxytryptamine (HT) from enterochromaffin cells; 5-HT acts via 5-HT4 receptors in rat and human, and via both 5-HT4 and 5-HT3 receptors in guinea pig to activate intramural sensory neurons that release calcitonin gene-related peptide. In this study, selective agonists and antagonists were used to examine the involvement of 5-HT4 and 5-HT3 receptors in colonic propulsion. The velocity of propulsion was measured with artificial fecal pellets introduced into the orad end of an isolated guinea pig colonic segment. Control velocity ranged from 0.5 to 3.3 mm/s; mean +/- S.E.M., 1.3 +/- 0.1 mm/s. The 5-HT4 antagonist, GR 113808A, and the 5-HT3 antagonist, LY 278584, decreased the velocity of pellet propulsion in a concentration-dependent fashion (39 +/- 2% and 47 +/- 1% decrease at 10 microM, respectively). A combination of both antagonists (10 microM each) was additive, decreasing the velocity by 82 +/- 3% to 84 +/- 4%. The selective 5-HT4 agonists, HTF 919 and R093877, as well as 5-HT in the presence of the 5-HT2a antagonist, ketanserin, increased the velocity of propulsion in a concentration-dependent fashion with EC50s of 6.9 +/- 0.1 nM, 37.4 +/- 1.0 nM, and 3.9 +/- 0. 1 nM, respectively. Compared with HTF 919, R093877 was less potent and appeared to be a partial agonist. All three agonists were effective at submicromolar concentrations; at concentrations above 1 microM, there was no increase in the velocity of propulsion. We conclude that the presence of fecal pellets triggers the release of 5-HT, which acts via both 5-HT3 and 5-HT4 receptors to regulate propulsive activity in guinea pig colon.