Cyclic nucleotides, gut physiology and inflammation.

Misregulation of gut function and homeostasis impinges on the overall well-being of the entire organism. Diarrheal disease is the second leading cause of death in children under 5 years of age, and globally, 1.7 billion cases of childhood diarrhea are reported every year. Accompanying diarrheal episodes are a number of secondary effects in gut physiology and structure, such as erosion of the mucosal barrier that lines the gut, facilitating further inflammation of the gut in response to the normal microbiome. Here, we focus on pathogenic bacteria-mediated diarrhea, emphasizing the role of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate in driving signaling outputs that result in the secretion of water and ions from the epithelial cells of the gut. We also speculate on how this aberrant efflux and influx of ions could modulate inflammasome signaling, and therefore cell survival and maintenance of gut architecture and function.

Defying the stereotype: non-canonical roles of the Peptide hormones guanylin and uroguanylin.

The peptide hormones uroguanylin and guanylin have been traditionally thought to be mediators of fluid-ion homeostasis in the vertebrate intestine. They serve as ligands for receptor guanylyl cyclase C (GC-C), and both receptor and ligands are expressed predominantly in the intestine. Ligand binding to GC-C results in increased cyclic GMP production in the cell which governs downstream signaling. In the last decade, a significant amount of research has unraveled novel functions for this class of peptide hormones, in addition to their action as intestinal secretagogues. An additional receptor for uroguanylin, receptor guanylyl cyclase D, has also been identified. Thus, unconventional roles of these peptides in regulating renal filtration, olfaction, reproduction, and cell proliferation have begun to be elucidated in detail. These varied effects suggest that these peptide hormones act in an autocrine, paracrine as well as endocrine manner to regulate diverse cellular processes.