鸟苷酸环化酶C：当前的热点，从生理学到病理学。,Current Medicinal Chemistry

当前位置： X-MOL 学术 › Curr. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

鸟苷酸环化酶C：当前的热点，从生理学到病理学。
Current Medicinal Chemistry ( IF 3.5 ) Pub Date : 2017-12-07 , DOI: 10.2174/0929867325666171205150310
Jose Antonio Uranga _{1,

2,

3} , Marta Castro _{4,

5,

6} , Raquel Abalo _{1,

2,

3,

7}

Affiliation

背景技术鸟苷酸环化酶C（GC-C）受体是一种跨膜受体，主要在肠上皮细胞中表达，被认为在体内稳态和消化道功能中起主要作用。该受体的内源性配体是旁分泌激素尿鸟苷和鸟苷。配体结合后，GC-C受体会增加环状鸟苷单磷酸（cGMP）的水平，从而调节各种关键细胞类型的特定过程，例如氯化物和碳酸氢盐的分泌，上皮细胞的生长，肠道屏障完整性和内脏敏感性的调节。已经提出GC-C充当肠肿瘤抑制剂，具有预防结直肠癌的发生和发展的潜力。实际上，配体表达的丧失是散发性结直肠癌发生中的普遍步骤。有趣的是，GC-C的作用不仅限于消化道，它还扩展到了其他几个系统，例如心血管系统，肾脏和中枢神经系统，这些系统都参与了肠下丘脑内分泌轴调节食欲。目的：在本综述中，我们总结了GC-C受体及其配体的生理特性，重点研究了利那洛肽等新近开发的药物，以及它们在逆转/预防该受体所涉及疾病方面的建议作用。结论现有数据指出了尿鸟苷蛋白和鸟苷蛋白及其受体与胃肠道和肾脏疾病，结肠直肠癌，肥胖症，代谢综合征和精神疾病等病理过程之间的关系。

"点击查看英文标题和摘要"

Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology.

BACKGROUND Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, which is considered to play a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. Upon ligand binding, GC-C receptors increase cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion, epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity. It has been suggested that GC-C acts as an intestinal tumor suppressor with the potential to prevent the initiation and progression of colorectal cancer. In fact, loss of ligand expression is a universal step in sporadic colorectal carcinogenesis. Interestingly, the role of GC-C is not limited to the digestive tract but it has been extended to several other systems such as the cardiovascular system, kidney, and the central nervous system, where it has been involved in a gut-hypothalamus endocrine axis regulating appetite. Objetive: In this review we summarize the physiology of the GC-C receptor and its ligands, focusing on newly developed drugs like linaclotide, and their suggested role to reverse/prevent the diseases in which the receptor is involved. CONCLUSION Available data points toward a relationship between uroguanylin and guanylin and their receptor and pathological processes like gastrointestinal and renal disorders, colorectal cancer, obesity, metabolic syndrome and mental disorders among others. Recent pharmacological developments in the regulation of GC-receptor may involve further improvements in the treatment of relevant diseases.

更新日期：2019-11-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南