Kuemmerle J F, Smith E H, Borum E H, Kellum J M
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0161.
J Surg Res. 1988 Jun;44(6):740-4. doi: 10.1016/0022-4804(88)90109-6.
We have previously documented predominant intraluminal release of serotonin (5-HT) following activation of muscarinic receptors on enterochromaffin cells. Gronstad et al. reported that portal venous release of 5-HT in response to vagal stimulation was mediated by beta-adrenergic receptors. The purpose of this study was to determine whether 5-HT release induced by the beta-adrenergic agonist, isoproterenol, is mediated by enteric nerves or is a direct action at the enterochromaffin cell level. We mounted rabbit duodenal mucosal sheets stripped of muscularis in modified Ussing chambers and measured release of 5-HT in response to 10(-5) M isoproterenol, in the presence and absence of the neural conduction blocker tetrotoxin, 10(-6) M. Serotonin was measured in the buffer bathing the mucosal and submucosal surfaces by HPLC. In the presence of isoproterenol, total (mucosal and submucosal) 5-HT release (21.0 +/- 4.9 ng/cm2/45 min) was significantly (P less than 0.05) greater than that in untreated controls (7.8 +/- 2.7 ng/cm2/45 min); release was predominantly toward the submucosal surface. In the presence of tetrodotoxin alone, net 5-HT release was significantly (P less than 0.05) increased to 12.8 +/- 2.8 ng/cm2/45 min. In tetrodotoxin-treated mucosa, isoproterenol increased 5-HT release to 28.6 +/- 5.3 ng/cm2/45 min which was significantly greater (P less than 0.05) than that with tetrodotoxin alone. Since 5-HT release was increased even in the presence of neural blockade, these results suggest that activation of beta-adrenergic receptors on or near enterochromaffin cells induces release of 5-HT predominantly toward the submucosal surface.
我们之前已记录到，肠嗜铬细胞上的毒蕈碱受体激活后，血清素（5-羟色胺，5-HT）主要在管腔内释放。格伦斯塔德等人报告称，迷走神经刺激引起的门静脉5-HT释放是由β-肾上腺素能受体介导的。本研究的目的是确定β-肾上腺素能激动剂异丙肾上腺素诱导的5-HT释放是由肠神经介导的，还是在肠嗜铬细胞水平上的直接作用。我们在改良的尤斯廷斯小室中安装了去除肌层的兔十二指肠黏膜片，并在存在和不存在神经传导阻滞剂10(-6) M河豚毒素的情况下，测量了对10(-5) M异丙肾上腺素的反应中5-HT的释放。通过高效液相色谱法测定黏膜和黏膜下表面缓冲液中的血清素。在存在异丙肾上腺素的情况下，总的（黏膜和黏膜下）5-HT释放量（21.0±4.9 ng/cm2/45分钟）显著（P<0.05）高于未处理的对照组（7.8±2.7 ng/cm2/45分钟）；释放主要朝向黏膜下表面。仅在存在河豚毒素的情况下，5-HT的净释放量显著（P<0.05）增加至12.8±2.8 ng/cm2/45分钟。在经河豚毒素处理的黏膜中，异丙肾上腺素将5-HT释放量增加至28.6±5.3 ng/cm2/45分钟，这显著（P<0.05）高于仅使用河豚毒素时的释放量。由于即使在存在神经阻滞的情况下5-HT释放仍增加，这些结果表明肠嗜铬细胞上或其附近的β-肾上腺素能受体激活主要诱导5-HT向黏膜下表面释放。
