Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model
Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model
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DOI：
10.1053/j.gastro.2004.04.070
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发表时间：
2004-07-01
期刊：
影响因子：
29.4
通讯作者：
Cooke, HJ
中科院分区：
文献类型：
--
作者：
Christofi, FL;Kim, M;Cooke, HJ
背景与目的：探讨腺苷受体对人类癌Bon细胞内cAMP、细胞内游离钙([Ca+](I))和5-羟色胺(5-HT)释放的调节作用。方法：用Western blotts、免疫荧光标记、Fluo-4/AM[Ca~(2+)](I)显像法和药理学/生理学技术鉴定腺苷受体(R)的mRNA、蛋白质和功能。结果：A1、A2和A3Rs在Bon细胞和类癌中均有表达。基线5-羟色胺水平随着腺苷脱氨酶、A2Rs的激活和A3Rs的抑制而升高，而A3R的激活则降低了5-羟色胺。A2R拮抗剂或阻断腺苷再摄取可提高细胞外腺苷水平，从而减少机械诱导的5-羟色胺释放。在Single Bon细胞中，腺苷脱氨酶、A1和A3R拮抗剂可增强触摸升高的[钙](I)反应。结论：内源性腺苷的紧张性或机械诱发释放是腺苷受体差异激活的关键决定因素，可能对肠道机械感觉反射有重要意义。
Background & Aims: The aim was to determine whether adenosine receptors modulate CAMP, intracellular free calcium ([Ca2+](i)), and 5-hydroxytrypta mine (5-HT) release in human carcinoid BON cells. Methods: Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca2+](i) imaging, and pharmacologic/ physiologic techniques. Results: A1, A2, and A3Rs were present in BON cells and carcinoid tumors. Baseline 5-HT levels increased with adenosine deaminase, activation of A2Rs, and inhibition of A3Rs, whereas A3R activation decreased 5-HT. A2R antagonists or blockade of adenosine reuptake that elevates extracellular adenosine reduced mechanically evoked 5-HT release. In single BON cells, touch elevated [Ca2+](i) responses were augmented by adenosine deaminase, A1, and A3R antagonists. Conclusions: Tonic or mechanically evoked release of endogenous adenosine is a critical determinant of differential activation of adenosine receptors and may have important implications for gut mechanosensory reflexes.