Arin Rosa María, Vallejo Ana Isabel, Rueda Yuri, Fresnedo Olatz, Ochoa Begoña
Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain
Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa, Spain.
Am J Physiol Cell Physiol. 2015 Dec 15;309(12):C823-34. doi: 10.1152/ajpcell.00224.2015. Epub 2015 Oct 14.
Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four G protein-coupled receptors. The renewed interest in the adenosine A2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A2 adenosine receptor subtype(s) on the cell surface. Recently, we confirmed A2BR expression in native, nontransformed parietal cells at rest by using flow cytometry and confocal microscopy. In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased adenylate cyclase activity and acid production. In addition, both acid production and radioligand binding of adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas ligands for A1, A2A, and A3 adenosine receptors failed to abolish activation. We conclude that rabbit gastric parietal cells possess functional A2BR proteins that are coupled to Gs and stimulate HCl production upon activation. Whether adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated.
腺苷可调节胃肠道许多细胞中的不同功能活动；其中一些活动被认为是通过与其四种G蛋白偶联受体相互作用介导的。对腺苷A2B受体（A2BR）亚型重新产生的兴趣可以追溯到一些研究，在这些研究中，新的基因和化学工具的引入拓宽了对该受体的药理学和结构知识，以及其在癌症和炎症或缺氧相关病理中的潜在治疗用途。在胃黏膜分泌酸的壁细胞中，使用各种腺苷受体放射性配体表明细胞表面存在A2腺苷受体亚型。最近，我们通过流式细胞术和共聚焦显微镜证实了静息状态下天然未转化壁细胞中A2BR的表达。在本研究中，我们表明A2BR在原代兔胃壁细胞中具有功能，这一事实表明激动剂与A2BR结合可增加腺苷酸环化酶活性和酸分泌。此外，酸分泌以及腺苷类似物与分离细胞膜的放射性配体结合均被选择性A2BR拮抗剂有效阻断，而A1、A2A和A3腺苷受体的配体未能消除这种激活。我们得出结论，兔胃壁细胞具有与Gs偶联的功能性A2BR蛋白，激活后可刺激盐酸分泌。腺苷和A2BR介导的功能反应是否在人类胃病理生理学中起作用尚待阐明。
