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首页> 外文期刊>American Journal of Physiology >The role of mechanical forces and adenosine In the regulation of intestinal enterochromaffin cell serotonin secretion
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The role of mechanical forces and adenosine In the regulation of intestinal enterochromaffin cell serotonin secretion

机译：机械力和腺苷在肠道小肠嗜铬细胞5-羟色胺分泌调节中的作用

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Enterochromaffin (EC) cells of the diffuse neuroendocrine cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitiv-ity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98-99%) FACS-sorted normal and IBD human EC cells and neo-plastic EC cells (KRJ-I) were studied. IBD-EC cells and KRJ-I overexpressed ADORA2B. NEC A, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS 1754 inhibited, 5-HT release (EC_50 = 1.8 X 10~6 M; IC_50 = 3.7 X 10~8 M), which was associated with corresponding alterations in intracel-lular cAMP levels and pCREB (Serl33). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMATi (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS 1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tphl and VMATi transcription was regulated by PKA/MAPK and PI_3K-mediated signaling. Normal and IBD-EC cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC cell function are necessary for understanding its role as a mechanosensory cell and to facilitate the development of agents that can selectively target cell function in EC cell-associated disease.
机译：弥漫性神经内分泌细胞系统的肠嗜铬细胞（EC）细胞分泌5-羟色胺（5-HT），并激活肠蠕动，分泌和疼痛。这些细胞表达腺苷（ADORA）受体，并被认为可以充当机械传感器。介导机械敏感性和腺苷反应性的生理途径，以及它们在炎症性肠病（IBD）和瘤形成中的作用，仍需充分阐明。研究了纯的（98-99％）FACS分选的正常和IBD人EC细胞和赘生性EC细胞（KRJ-1）。 IBD-EC细胞和KRJ-1过表达ADORA2B。普通的ADORA受体激动剂NECA受到刺激，而A2B受体拮抗剂MRS 1754抑制5-HT释放（EC_50 = 1.8 X 10〜6 M; IC_50 = 3.7 X 10〜8 M），这与相应的改变有关细胞内cAMP水平和pCREB（Serl33）。使用节律性屈曲模型进行机械刺激可诱导Tph1（色氨酸羟化酶）和VMATi（水泡单胺转运蛋白1）的转录和激活以及5-HT的释放，这可能受MRS 1754抑制并被NECA放大。 H-89（PKA抑制剂）也抑制了分泌，而Tph1和VMATi的转录受PKA / MAPK和PI_3K介导的信号传导调节。正常细胞和IBD-EC细胞也通过PKA激活，cAMP产生和5-HT释放来响应NECA和机械刺激，这是MRS1754可逆的。 EC细胞表达刺激性ADORA2B，节律性伸展诱导5-HT合成和分泌的A2B活化，PKA / MAPK / IP3依赖性转录和PKA依赖性分泌。受体表达在IBD和瘤形成中被扩增，并且5-HT释放增加。确定调节EC细胞功能的因素对于了解其作为机械感觉细胞的作用并促进可选择性靶向EC细胞相关疾病中细胞功能的药物的开发是必要的。

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