Title:Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology
Volume: 25
Issue: 16
Author(s): Jose Antonio Uranga, Marta Castro and Raquel Abalo*
Affiliation:
- Depto. de Ciencias Basicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid,Spain
Keywords:
Guanylate cyclase C, heat-stable enterotoxin, diarrhea, irritable bowel syndrome, constipation, colorectal
cancer, obesity, inflammatory bowel disease.
Abstract: 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.
