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)

Enterotoxin derived from three clinical isolates of Yersinia enterocolitica was compared with the heat-stable enterotoxin of Escherichia coli. Both toxins were biologically active in infant mice examined at 2 h and in ligated rabbit ileal loops at 6 h. Neither substance, however, produced changes in ligated ileal loops at 18 h or in Chinese hamster ovary or Y1 adrenal tissue cultures. In addition, both Y. enterocolitica enterotoxin concentrated approximately 20 times by ammonium sulfate precipitation and ultrafiltration and a similarly prepared sample of E. coli heat-stable enterotoxin stimulated the activity of guanylate cyclase but not that of adenylate cyclase in infant mouse intestine. These findings suggest that the role of enterotoxin in the pathogenesis of intestinal Y.enterocolitica infection may be similar to that of heat-stable enterotoxin in E. coli diarrhea.
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PMID:Mechanism of action of Yersinia enterocolitica enterotoxin. 3 94

Strains of Yersinia enterocolitica produce a heat-stable enterotoxin which is positive in the suckling mouse bioassay. Partial purification by a procedure previously worked out for heat-stable Escherichia coli enterotoxin yielded a substance which increases particulate guanylate cyclase activity and short-circuit current and inhibits active Cl-absorption in rabbit ileal mucosa. These effects of Y. enterocolitica enterotoxin are similar to those of heat-stable E. coli enterotoxin, suggesting a common mechanism of action.
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PMID:Effects of heat-stable enterotoxin of Yersinia enterocolitica on ion transport and cyclic guanosine 3',5'-monophosphate metabolism in rabbit ileum. 4 92

Heat-stable enterotoxins (ST) activate guanylyl cyclase in T84 cells, rapidly and specifically. Activation is monitored by cGMP production and occurs at lower concentrations of ST than required for eliciting fluid accumulation in suckling mice. Atrial natriuretic factor (ANF) neither activates guanylyl cyclase nor modulates the response to ST in T84 cells, indicating the absence of receptors for ANF on T84 cells. Monitoring the production of cGMP under conditions known to alter fluid accumulation in suckling mice is an accurate and quantifiable assay of ST activity and its interaction with the receptor. STs produced by Escherichia coli, Vibrio cholerae non-01 and Yersinia enterocolitica individually produce elevated levels of cGMP in T84 cells, but to differing extents, suggesting that this model system can be used to elucidate the different events of ST-receptor interactions at the molecular level.
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PMID:Interaction of heat-stable enterotoxins with human colonic (T84) cells: modulation of the activation of guanylyl cyclase. 135 30

In spite of the resemblance of the clinical picture of gastrointestinal yersiniosis and acute dysentery, material differences underlie the pathogenesis of these diseases. Yersiniosis is marked by the predominance of an increase in the content of PGF2 alpha, whereas acute dysentery by an increase in the content of PGE, which may be accounted for by greater intensity of the allergic manifestations in yersiniosis patients as compared with dysentery. Shigellosis runs its course in the presence of the prevailing influence of the guanylate cyclase system, whereas yersiniosis in that of the adenylate cyclase. This is likely to be related to graver destructive lesions in the colonic mucosa in acute dysentery.
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PMID:[Prostaglandins and cyclic nucleotides in the gastrointestinal form of yersiniosis]. 269 95

Certain enteropathogenic bacteria, including strains of Escherichia coli, Klebsiella pneumoniae and Yersinia enterocolitica, elicit their diarrhoeagenic effects by elaborating small molecular weight, heat-stable enterotoxins (STs). Structural and functional characteristics indicate that ST peptides are heterogeneous and two major subtypes, STa and STb, have been identified. Molecules of STa, unlike those of STb, are methanol-soluble and elicit their pathogenic effects by activating host cell guanylate cyclase activity and thereby increasing tissue cyclic GMP content: this increase in cyclic GMP causes fluid secretion. STa binds to specific proteinaceous receptors on intestinal cells but the nature of STa-receptor coupling to guanylate cyclase is poorly understood. The actions of STa, including binding to its receptor, activation of guanylate cyclase and stimulation of electrolyte transport, are rapid, reversible and tissue-specific. STa activates only particulate and not soluble guanylate cyclase. It alters the Vmax but not the apparent Km of this enzyme for Mg-GTP or Mn-GTP. At concentrations above 0.5-1 mM, calcium inhibits the STa activation of guanylate cyclase. The effects of calmodulin antagonists such as chlorpromazine on the activation of guanylate cyclase by STa are less clear. Inhibitors of phospholipid and arachidonic acid cascade pathways interfere with both basal and STa-stimulated guanylate cyclase. Membrane integrity is essential for STa activation of guanylate cyclase and the STa-receptor complex may activate the enzyme by intramembrane protein-protein interactions and/or perturbations. Interference with membrane phospholipid could alter such coupling.
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PMID:Toxins which activate guanylate cyclase: heat-stable enterotoxins. 286 Oct 70

Recent studies have added important new information to our understanding of the pathogenesis and ethiology of diarrheal disease. Vibrio cholerae produces a heat-labile enterotoxin, affecting cyclic AMP. A very similar heat-labile enterotoxin is produced also by certain strains of Escherichia coli, as well as by Citrobacter, Klebsiella, and Aeromonas. E. coli may also produce a heat-stable enterotoxin, stimulating guanylate cyclase activity. In order to produce the pathologic effects, E. coli first attaches to epithelial cells of the intestinal tract by means of pili or surface antigens. Enterotoxin can be demonstrated by both in vivo and in vitro tests, but none are yet suitable for routine diagnostic laboratories. A third mechanism whereby E. coli causes diarrheal disease consists of enteroinvasiveness. Campylobacter, Yersinia, and Clostridium difficile have been added to the list of enteric pathogens of man.
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PMID:Enteropathogenicity: recent developments. 612 11

Yersinia pestis toxin (II fraction by E. Baker) inhibited aggregation of human platelets as well as elevation of Ca2+, induced by different agonists ADP, PAF, thrombin. Agonist-induced Ca2+ mobilization and Ca2+ influx were dose-dependently inhibited by the toxin. The effect was rapid, developing during the first minute of incubation with the toxin. In contrast to murine lethal protein the platelet inhibitory activity was thermostable. The action of thermostable factor on platelets was accompanied by elevation of cellular cGMP level. This factor of Y. pestis activated guanylate cyclase in human platelets.
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PMID:[Features of regulatory system function in platelets under the effect of plague toxin]. 761 91

Thermostable protein factor (20000 Da) was prepared from Yersinia pestis avirulent strain EV 1290. This protein inhibited the aggregation of human platelets as well as elevation of [Ca2+], induced by different agonist. The action of this protein on platelets is accompanied by elevation of cellular cGMP levels. This factor activated guanylate cyclase suspension of human platelets. The data indicate that this protein factor of Y. pestis may possibly release in circulation during decay of bacteria and can change the physiological activity of human blood cells and contribute to the pathogenesis of plague.
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PMID:[The mechanism of the inhibiting effect of a Yersinia pestis protein factor on the hormone-stimulated response of human thrombocytes]. 831 51

Yersinia enterocolitica is a well-known foodborne pathogen causing gastrointestinal infections worldwide. The strain Y. enterocolitica FORC_002 was isolated from the gill of flatfish (plaice) and its genome was sequenced. The genomic DNA consists of 4,837,317 bp with a GC content of 47.1%, and is predicted to contain 4,221 open reading frames, 81 tRNA genes, and 26 rRNA genes. Interestingly, genomic analysis revealed pathogenesis and host immune evasion-associated genes encoding guanylate cyclase (Yst), invasin (Ail and Inv), outer membrane protein (Yops), autotransporter adhesin A (YadA), RTX-like toxins, and a type III secretion system. In particular, guanylate cyclase is a heat-stable enterotoxin causing Yersinia-associated diarrhea, and RTX-like toxins are responsible for attachment to integrin on the target cell for cytotoxic action. This genome can be used to identify virulence factors that can be applied for the development of novel biomarkers for the rapid detection of this pathogen in foods.
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PMID:Genomic Insights and Its Comparative Analysis with Yersinia enterocolitica Reveals the Potential Virulence Determinants and Further Pathogenicity for Foodborne Outbreaks. 2797 37