Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. The intestinal peptide guanylin is ideally suited to play a pivotal role in this regulation. Guanylin is produced by the epithelium and appears to be secreted mucosally to act locally on an apical receptor. The guanylin receptor is a member of the guanylate cyclase (GC-C) family of proteins. Elevation of intracellular cyclic GMP by guanylin mediates the stimulation of Cl- secretion, which results in the increased intestinal fluid secretion. Proguanylin is found in the circulation and GC-C occurs in other epithelia, suggesting that guanylin plays an endocrine role by regulating the function of tissues such as the kidney and liver. Uroguanylin is a structurally related peptide that is abundant in urine, has biological activity similar to guanylin, and appears to be made by the intestine. This peptide may link the intestine and kidney in an endocrine pathway for control of renal salt excretion. Overproduction of guanylin/uroguanylin would be expected to elicit secretory diarrhea similar to that caused by the bacteria that produce peptide analogs of these endogenous peptide hormones. This unique molecular mimicry has provided clues leading to the discovery of guanylin and insight into the mechanism of action of these intestinal peptides. The discoveries of guanylin and uroguanylin have provided exciting opportunities for further enhancing our understanding of epithelial transport and function.
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PMID:Guanylin: a peptide regulator of epithelial transport. 776 56

Guanylin and uroguanylin are novel peptides that are first isolated from rat jejunum and opossum urine, respectively. They bind to and activate guanylyl cyclase-C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cyclic 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 in the intestine are secreted into the lumen and blood in response to sodium chloride administration. These peptides will function in salt and water transport in the intestine and kidney by luminocrine and/or endocrine actions. Guanylin peptide family links the intestine with the kidney and could play the physiological roles in the control of water and electrolyte balance.
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PMID:[Guanylin family: new intestinal peptides regulating salt and water homeostasis]. 978 Jul 32

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.
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PMID:Guanylin family: new intestinal peptides regulating electrolyte and water homeostasis. 1132 23

Diverse color patterns on the integument of lepidopteran larvae play important roles in their survival through camouflage, mimicry, sexual signaling, and aposematism. In the silkworm Bombyx mori, many color pattern variations have been preserved in inbred strains making them a good model for elucidating the molecular mechanisms that underlie color pattern formation. In this study, we focused on the silkworm quail (q) mutant, which exhibits abnormalities in multiple pigment biosynthesis pathways. Positional cloning of the q gene revealed that disruption of a guanylyl cyclase gene, BmGC-I, is responsible for its abnormal pigmentation. In q mutants, we identified a 16-bp deletion in the BmGC-I transcript, resulting in the production of a premature stop codon. Knockout of the BmGC-I gene resulted in the q-like abnormal pigmentation, thereby demonstrating that the BmGC-I gene is involved in the pigment biosynthesis pathway in the integument. Moreover, quantitative reverse transcription polymerase chain reaction showed that BmGC-I was strongly expressed in the fourth instar on day 2. Our results suggest that BmGC-I deficiency affects the pigment biosynthesis pathway, which supports the involvement of guanylyl cyclase in larval coloration.
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PMID:Identification of the silkworm quail gene reveals a crucial role of a receptor guanylyl cyclase in larval pigmentation. 2656 Dec 70