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[小鼠回肠隐窝中肠嗜铬细胞血清素释放的信号转导]

[Signal transduction of serotonin release from enterochromaffin cells in mouse ileal crypts].

作者信息

Hirafuji M, Kato K, Suzuguchi T, Ogawa T, Endo T, Satoh Y, Minami M

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1998 Oct;112 Suppl 1:133P-137P. doi: 10.1254/fpj.112.supplement_133.

Abstract

Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered to be regulated by multiple receptor-mediated mechanisms, little is known about the signal transduction in EC cells. We investigated the effects of adrenoceptor stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in organ bath were perfused with a buffered solution. Released 5-HT was measured using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by moderate pipetting. Intracellular calcium dynamics were analyzed by digital video-imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a transient elevation of intracellular calcium in some EC cells. The effect of NE (1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM significantly induced an increase in intracellular calcium concentration. NE-induced intracellular calcium dynamics was not significantly affected by timolol, Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT release from ileal EC cells is mediated predominantly via alpha 2-, but not beta-adrenoceptors, by a mechanism dependent on elevation of intracellular calcium concentration.

摘要

尽管人们认为肠嗜铬(EC)细胞释放5-羟色胺(5-HT)受多种受体介导机制的调节,但对EC细胞中的信号转导却知之甚少。我们研究了肾上腺素能受体刺激对小鼠回肠组织5-HT释放及离体回肠隐窝上皮细胞内钙动力学的影响。置于器官浴中的回肠组织用缓冲溶液灌注。使用高效液相色谱-电化学检测法(HPLC-ECD)测定释放的5-HT。通过胶原酶消化并适度吹打分离回肠隐窝。使用fura-2通过数字视频成像系统分析细胞内钙动力学。去甲肾上腺素(NE)而非异丙肾上腺素(Iso)可诱导小鼠回肠组织释放5-HT。育亨宾和萝芙木碱可拮抗NE诱导的5-HT释放,而哌唑嗪和布那唑嗪则不能。NE而非Iso也可引起一些EC细胞内钙的短暂升高。哌唑嗪和布那唑嗪可轻微抑制NE(1 microM)的作用,而育亨宾和萝芙木碱则可显著抑制其作用。10 microM的UK 14,304和可乐定可显著诱导细胞内钙浓度升高。NE诱导的细胞内钙动力学不受噻吗洛尔、Ro20-1724、咯利普兰和8-溴-cAMP的显著影响。这些结果表明,NE诱导回肠EC细胞释放5-HT主要通过α2-肾上腺素能受体介导,而非β-肾上腺素能受体,其机制依赖于细胞内钙浓度的升高。

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