5-hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine
5-hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine
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DOI：
10.1016/s0016-5085(98)70203-3
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发表时间：
1998-08-01
期刊：
影响因子：
29.4
通讯作者：
Jin, JG
中科院分区：
文献类型：
--
作者：
Grider, JR;Foxx-Orenstein, AE;Jin, JG
背景与目的：粘膜刺激诱导的蠕动反射是由肠嗜铬细胞释放的 5-羟色胺 (5-HT) 激活的内在感觉降钙素基因相关肽 (CGRP) 神经元介导的。用选择性 5-HT4 激动剂检查 5-HT4 受体的参与情况。方法：使用隔室肠段来测量神经递质释放和反射的机械成分。结果：在人空肠、大鼠和豚鼠结肠段中，添加 5-HT4 激动剂 HTF 919 引起 CGRP 仅释放到添加了 5-HT4 激动剂的隔室中；血管活性肠肽（VIP）仅释放到测量下降舒张的室中，并且P物质（SP）仅释放到测量上升收缩的室中。 CGRP 拮抗剂 hC-GRP8-37 将两种机械反应抑制 75%-80%。 CGRP、VIP 和 SP 的释放以及上升和下降反应被选择性 5-HT4 抑制，但不被选择性 5-HT3 拮抗剂抑制。使用不同的 5-HT4 激动剂 R093877 也获得了类似的结果。然而，HTF 919 的效力（中位有效浓度，类似于肽释放的 10 nmol/L 和机械反应的 5 nmol/L）比 R093877 强 10-30 倍。结论：以纳摩尔浓度应用于粘膜的选择性 5-HT4 激动剂可触发人、大鼠和豚鼠肠道的蠕动反射。
Background & Aims: The peristaltic reflex induced by mucosal stimuli is mediated by intrinsic sensory calcitonin gene-related peptide (CGRP) neurons activated by 5-hydroxytryptamine (5-HT) released from enterochromaffin cells. The involvement of 5-HT4 receptors was examined with selective 5-HT4 agonists. Methods: Compartmented intestinal segments were used to measure neurotransmitter release and the mechanical components of the reflex. Results: In human jejunal and rat and guinea pig colonic segments, addition of the 5-HT4 agonist HTF 919 elicited release of CGRP only into the compartment where the 5-HT4 agonist was added; vasoactive intestinal peptide (VIP) was released only into the compartment where descending relaxation was measured, and substance P (SP) was released only into the compartment where ascending contraction was measured. The CGRP antagonist hC-GRP8-37 inhibited both mechanical responses by 75%-80%. Release of CGRP, VIP, and SP as well as ascending and descending responses were inhibited by selective 5-HT4 but not by selective 5-HT3 antagonists. Similar results were obtained with a different 5-HT4 agonist, R093877. However, HTF 919 was 10-30 times more potent (median effective concentration, similar to 10 nmol/L for peptide release and 5 nmol/L for mechanical responses) than R093877. Conclusions: Selective 5-HT4 agonists applied to the mucosa in nanomolar concentrations trigger the peristaltic reflex in human, rat, and guinea pig intestine.