鸟苷酸环化酶C：当前从生理学到病理学备受关注的研究目标

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

Volume: 25 Issue: 16

关键词: 鸟苷酸环化酶C，热稳定肠毒素，腹泻，肠易激综合征，便秘，结肠直肠癌，肥胖症，炎症性肠病。

摘要: 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.

Cite this article as:

Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology, Current Medicinal Chemistry 2018; 25 (16) . https://dx.doi.org/10.2174/0929867325666171205150310