An Enhanced cAMP Pathway Is Responsible for the Colonic Hyper-Secretory Response to 5-HT in Acute Stress Rats
An Enhanced cAMP Pathway Is Responsible for the Colonic Hyper-Secretory Response to 5-HT in Acute Stress Rats
复制标题
增强的 cAMP 通路是急性应激大鼠结肠对 5-HT 的过度分泌反应的原因。
DOI：
10.33549/physiolres.932863
复制
发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Zhu, J. X.
中科院分区：
文献类型：
--
作者：
Li, Y.;Li, L. S.;Zhu, J. X.
5-羟色胺（5-HT）参与应激诱导的结肠功能改变，特别是运动和分泌，但其确切的调节机制尚不清楚。在本研究中，我们研究了5-HT对急性水浸束缚应激后大鼠结肠粘膜分泌的影响，以及这种现象的潜在机制，采用短路电流记录（I（SC）），实时聚合酶链反应，蛋白质印迹分析，酶联免疫吸附试验。水浸束缚应激2 h后，结肠粘膜的基础I（SC）和5-HT诱导的I（SC）反应均显著增加。用选择性5-HT（4）受体拮抗剂SB 204070预处理，可使正常大鼠和急性应激大鼠的结肠I（SC）反应分别抑制96%和91.2%。然而，5-HT（3）受体选择性拮抗剂MDL 72222或Y-25130预处理对5-HT诱导的I（SC）反应无明显影响。急性应激后，粘膜5-HT（3）受体和5-HT（4）受体的总蛋白表达没有明显变化。结肠基础cAMP水平和福斯可林诱导的I（SC）反应在急性应激大鼠显着增强。5-HT可通过5-HT（4）受体使对照组和应激组大鼠结肠粘膜细胞内cAMP水平显著升高，但应激组大鼠5-HT诱导的cAMP水平升高幅度并不高于对照组。两者合计，本研究结果表明，急性水浸束缚应激增强结肠分泌反应，5-HT在大鼠中，一个过程中，增加细胞cAMP的积累参与。
5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (I(SC)), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline I(SC) and 5-HT-induced I(SC) responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT(4) receptor antagonist, SB204070, inhibited the 5-HT-induced colonic I(SC) response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT(3) receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced I(SC) responses under either set of conditions. Total protein expression of both the mucosal 5-HT(3) receptors and the 5-HT(4) receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced I(SC) responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT(4) receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved.