Guanylin and uroguanylin are peptides that activate guanylyl cyclase C (GC-C) receptors in the intestine and kidney, which causes an increase in the excretion of salt and water. The Spinifex hopping mouse, Notomys alexis, is a desert rodent that can survive for extended periods without free access to water and it was hypothesised that to conserve water, the expression of guanylin, uroguanylin, and GC-C would be down-regulated to reduce the excretion of water in urine and faeces. Accordingly, this study examined the expression of guanylin, uroguanylin, and GC-C mRNA in Notomys under normal (access to water) and water-deprived conditions. Initially, guanylin and uroguanylin cDNAs encoding the full open reading frame were cloned and sequenced. A PCR analysis showed guanylin and uroguanylin mRNA expression in the small intestine, caecum, proximal and distal colon, heart, and kidney. In addition, a partial GC-C cDNA was obtained and GC-C mRNA expression was demonstrated in the proximal and distal colon, but not the kidney. Subsequently, a semi-quantitative PCR method showed that water deprivation in Notomys caused a significant increase in guanylin and uroguanylin mRNA expression in the distal colon, and in guanylin and GC-C mRNA expression in the proximal colon. No significant difference in guanylin and uroguanylin mRNA expression was observed in the kidney. The results of this study indicate that there is, in fact, an up-regulation of the colonic guanylin system in Notomys after 7 days of water deprivation.
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http://dx.doi.org/10.1016/s0016-6480(03)00082-0 | DOI Listing |
J Pept Sci
January 2025
Graduate School of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan.
Guanylate cyclase C (GC-C), a receptor expressed on the apical membrane of intestinal mucosal cells, is activated by heat-stable enterotoxin (STa) produced by enterotoxigenic Escherichia coli, as well as the endogenous ligands guanylin and uroguanylin. In this study, novel peptides that interact with GC-C were generated using the cDNA display method, and their binding affinity and biological activity were evaluated. While the linear peptide library did not yield peptides with sufficient affinity for GC-C, three cyclic peptides (GCC-P1, GCC-P2, and GCC-P3), each containing two cysteine residues within a 15-residue sequence, were obtained from a cyclic peptide library containing nine-residue random sequences.
View Article and Find Full Text PDFJ Pept Sci
January 2025
Marine Biotechnology, NORCE Norwegian Research Centre, Bergen, Norway.
Enterotoxigenic Escherichia coli (ETEC) strains, which produce the heat-stable enterotoxin (ST) either alone or in combination with the heat-labile enterotoxin, contribute to the bulk of the burden of child diarrheal disease in resource-limited countries and are associated with mortality. Developing an effective vaccine targeting ST presents challenges due to its potent enterotoxicity, non-immunogenicity, and the risk of autoimmune reaction stemming from its structural similarity to the human endogenous ligands, guanylin, and uroguanylin. This study aimed to assess a novel synthetic vaccine carrier platform employing a single chemical coupling step for making human ST (STh) immunogenic.
View Article and Find Full Text PDFJ Biol Chem
January 2024
Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru, India. Electronic address:
Mutations in receptor guanylyl cyclase C (GC-C) cause severe gastrointestinal disease, including meconium ileus, early onset acute diarrhea, and pediatric inflammatory bowel disease that continues into adulthood. Agonists of GC-C are US Food and Drug Administration-approved drugs for the treatment of constipation and irritable bowel syndrome. Therapeutic strategies targeting GC-C are tested in preclinical mouse models, assuming that murine GC-C mimics human GC-C in its biochemical properties and downstream signaling events.
View Article and Find Full Text PDFFront Oncol
October 2023
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Introduction: Colorectal cancer (CRC) is a devastating disease that affects millions of people worldwide. Recent research has highlighted the crucial role of the guanylate cyclase-C (GC-C) signaling axis in CRC, from the early stages of tumorigenesis to disease progression. GC-C is activated by endogenous peptides guanylin (GU) and uroguanylin (UG), which are critical in maintaining intestinal fluid homeostasis.
View Article and Find Full Text PDFActa Stomatol Croat
September 2023
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia.
Objectives: Guanylin peptides are considered to be the only intrinsic regulators of salivary glands secretion. Therefore, the aim of this study was to determine the effects of systemic uroguanylin (UGN) of the salivary flow and ion composition. Besides, the objective was to investigate whether those effects include activation of guanylate cyclase C (GC-C).
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