Goldhill J, Porquet M F, Angel I
Department of Internal Medicine, Synthélabo Recherche, Rueil Malmaison, France.
Eur J Pharmacol. 1998 Jul 24;353(2-3):289-96. doi: 10.1016/s0014-2999(98)00420-8.
The present study characterized the rat colonic secretory response to 5-hydroxytryptamine (5-HT) and determined alterations in this response following stress. 5-HT stimulated rat colonic short-circuit current in a concentration-dependent fashion (pD2 = 5.19). This response was subject to desensitization and was mimicked by the indolealkylamines with a rank order potency of 5-HT approximately alpha-methyl-5-HT > 5-carboxytryptamine approximately 5-methoxytryptamine. 2-Methyl-5-HT was a partial agonist. The colonic response to 5-HT was unaltered by methysergide (10 microM), ritanserin (0.1 microM), ondansetron (1 microM) or clozapine (10 microM), but was antagonized by the 5-HT4 receptor antagonists SB204070 (pD'2 = 9.32), GR113808 (pKb = 8.56), DAU6285 (pKb = 6.07) and SDZ205557 (pKb = 6.80). The response of colonic epithelial and oesophageal tunica muscularis mucosae to 5-HT is therefore mediated by a similar 5-HT4 receptor. Following wrap restraint stress, the colonic response to 5-HT became bimodal. Half of the preparations were hyper-responsive, while the rest were hypo-responsive to 5-HT. This 5-HT4 receptor may therefore be involved in stress related changes in fluid transport.
本研究对大鼠结肠对5-羟色胺（5-HT）的分泌反应进行了表征，并确定了应激后该反应的变化。5-HT以浓度依赖性方式刺激大鼠结肠短路电流（pD2 = 5.19）。该反应会发生脱敏，且吲哚烷基胺可模拟此反应，其效力顺序为5-HT＞α-甲基-5-HT＞5-羧基色胺＞5-甲氧基色胺。2-甲基-5-HT是一种部分激动剂。结肠对5-HT的反应不受麦角新碱（10微摩尔）、利坦色林（0.1微摩尔）、昂丹司琼（1微摩尔）或氯氮平（10微摩尔）的影响，但被5-HT4受体拮抗剂SB204070（pD’2 = 9.32）、GR113808（pKb = 8.56）、DAU6285（pKb = 6.07）和SDZ205557（pKb = 6.80）拮抗。因此，结肠上皮和食管黏膜肌层对5-HT的反应是由相似的5-HT4受体介导的。束缚应激后，结肠对5-HT的反应变为双峰。一半的制剂反应增强，而其余的对5-HT反应减弱。因此，这种5-HT4受体可能参与了与应激相关的液体运输变化。
