کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5826389 | 1120431 | 2012 | 9 صفحه PDF | دانلود رایگان |
Guanylate cyclase-C (GC-C) is a transmembrane receptor activated by bacterial heat-stable enterotoxins and by the endogenous hormones guanylin and uroguanylin. GC-C plays key roles in the regulation of intestinal fluid and electrolyte homeostasis. This is highlighted by several recently identified human mutations in GUCY2C, the gene encoding GC-C, which leads to the respective gain or loss of function of GC-C, resulting in profound effects on gastrointestinal function. However, a wealth of recent studies indicates GC-C signalling extends to a multitude of diverse additional functions. Recent pre-clinical and clinical studies demonstrate a novel first-in-class GC-C activating peptide, Linaclotide, provides effective relief from constipation and abdominal pain in patients with chronic constipation and constipation-predominant Irritable Bowel Syndrome. Accumulating evidence also suggests GC-C plays protective roles in mucosal barrier function, tissue injury and inflammation, whilst GC-C signalling is a key regulator of intestinal cell proliferation and apoptosis. Finally, recently identified extra-intestinal GC-C signalling pathways make novel contributions to the regulation of food intake and symptoms associated with Attention Deficit Hyperactivity Disorder. Consequently, these findings provide GC-C expression and its associated mutations as potential diagnostic markers for disease. They also provide current and future therapeutic potential for GC-C signalling within and outside the gastrointestinal tract.
⺠GC-C is synonymous with regulating intestinal fluid and electrolyte homeostasis. ⺠Human mutations in GC-C lead to profound resultant effects on gastrointestinal motility. ⺠A new therapeutic agent utilizes GC-C mediated secretion for C-IBS and constipation treatment. ⺠GC-C signalling regulates intestinal barrier function, injury and inflammation. ⺠A GC-C dependent mechanism in the hypothalamus regulates food intake.
Journal: Current Opinion in Pharmacology - Volume 12, Issue 6, December 2012, Pages 632-640