Guanylin family: new intestinal peptides regulating electrolyte and water homeostasis

Abstract

The regulation of intestinal salt and water transport is critical to the maintenance of fluid volume. Control of this life-sustaining activity is mediated by the concerted actions of hormones, neurotransmitters, and locally acting factors. Guanylin and uroguanylin are novel peptides that were first isolated from rat jejunum and opossum urine, respectively. They bind to and activate guanylyl cyclase-C (GC-C) receptors to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cyclic guanosine 3',5'-monophosphate (GMP). Heat-stable enterotoxins produced by pathogenic bacteria have close structural similarities to guanylin and uroguanylin, and they use this mimicry to act on GC-C, causing life-threatening secretory diarrhea. Guanylin primarily is restricted to the intestine, whereas uroguanylin is present in the stomach, kidney, lung, and pancreas, in addition to intestine. Guanylin and uroguanylin are secreted into the intestinal lumen and blood in response to sodium chloride administration. These peptides function in salt and water transport in the intestine and kidney by luminocrine and endocrine actions. The guanylin family is involved in the pathophysiology of some gastrointestinal, renal, and heart diseases.