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)

The study was made on 59 chinchilla rabbits. S. typhimurium 1847 live culture was introduced into the lumen of an isolated loop of the thin intestine. The activity of adenylate cyclase (AC), guanylate cyclase (GC), the levels of cyclic adenosine 3,5-monophosphate (cAMP), cyclic guanosine 3,5-monophosphate (cGMP), the activity of cAMP- and cGMP-phosphodiesterases were determined in the mucous membrane of the ligated part of the intestine. Considerable fluid accumulation in the loop, activation of AC and cGMP-phosphodiesterase, a rise in the level of cAMP and a drop in the level of cGMP in the mucosa of the ligated part of the intestine were registered. In one group of the animals phosphadene and in the other group unitiol were introduced into the infected intestinal loop; as a result, a decrease in the accumulation of fluid in the loop, on the average, by 40% and a tendency to an increase in the level of cAMP and a drop in the level of cGMP in the mucous membrane of the ligated part of the intestine were observed. Changes in the level of cGMP play, seemingly, a more important role in the development of diarrhea in salmonellosis.
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PMID:[Effect of phosphaden and unithiol on the cyclase system of the small intestine mucosa in rabbits in experimental salmonellosis]. 289 50

From diarrheal diseases come profound lessons about health and population growth, microbial pathogenesis, and the molecular pharmacology of signal transduction. Epidemics such as cholera, hemorrhagic colitis, salmonellosis, and cryptosporidiosis remind us of how interdependent we are, sharing enteric microbial flora on a global scale. Diarrhea morbidity and mortality teach us that disease and poverty do not control but are associated with population overgrowth. Great advances are being made in understanding new bacterial, viral, and parasitic causes and treatment of diarrhea, especially persistent diarrhea. In addition, microbial toxins provide unique pharmacologic tools to probe cell signaling pathways. The mechanism of action of cholera toxin, once thought so clear, now appears to involve additional pathways such as platelet-activating factor and prostaglandin synthesis. Escherichia coli ST has opened a whole family of activators of guanylate cyclase, including new mammalian products that regulate sodium transport. Clostridium difficile toxin A provides a novel tool to dissect mediators involved in inflammatory diarrhea. These lessons have both basic implications for science and practical applications for medicine and society.
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PMID:Lessons from diarrheal diseases: demography to molecular pharmacology. 819 98

The guanylate cyclase C (GC-C) receptor regulates electrolyte and water secretion into the gut following activation by the E. coli enterotoxin STa, or by weaker endogenous agonists guanylin and uroguanylin. Our previous work has demonstrated that GC-C plays an important role in controlling initial infection as well as carrying load of non-invasive bacterial pathogens in the gut. Here, we use Salmonella enterica serovar Typhimurium to determine whether GC-C signaling is important in host defense against pathogens that actively invade enterocytes. In vitro studies indicated that GC-C signaling significantly reduces Salmonella invasion into Caco2-BBE monolayers. Relative to controls, GC-C knockout mice develop severe systemic illness following oral Salmonella infection, characterized by disrupted intestinal mucus layer, elevated cytokines and organ CFUs, and reduced animal survival. In Salmonella-infected wildtype mice, oral gavage of GC-C agonist peptide reduced host/pathogen physical interaction and diminished bacterial translocation to mesenteric lymph nodes. These studies suggest that early life susceptibility to STa-secreting enterotoxigenic E. coli may be counter-balanced by a critical role of GC-C in protecting the mucosa from non-STa producing, invasive bacterial pathogens.
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PMID:Guanylate cyclase C reduces invasion of intestinal epithelial cells by bacterial pathogens. 2936 34