Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.3.4.6 (urease)
7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral neurogenic vasodilation is mediated predominantly by nitric oxide (NO). Thus, NO was suggested to be a vasodilator transmitter. In the present study, the possibility that cerebral perivascular nerves can convert citrulline to arginine was examined to ascertain that NO is derived directly from these perivascular nerves. To investigate the uptake of citrulline and its conversion to arginine, both fresh and cold storage-denervated porcine cerebral arteries with or without endothelial cells were incubated at 37 degrees C for 2 hr in Krebs-Ringer bicarbonate buffer containing 0.5 mM purified [14C]ureido-citrulline. The formation of [14C]arginine was measured as 14CO2 by a coupled enzymatic assay involving arginase and urease. The abolishment of nitric oxidergic nerves was verified by NADPH-diaphorase (constitutive NO synthases) histochemical staining method. The results indicated that there was an active conversion of [14C]arginine from [14C]citrulline in nerve-intact arteries denuded of endothelial cells. The conversion was significantly decreased in denervated arteries, accompanied by a significantly reduced citrulline uptake into these denervated arteries. L-Glutamine, but not L-glutamate, gamma-aminobutyric acid, or nitro-L-arginine significantly inhibited the uptake of [14C]citrulline into cerebral perivascular nerves. These data suggest that porcine cerebral vasodilator nerves are nitric oxidergic in nature and citrulline, co-produced with NO by NO synthases from arginine, can be recycled to form arginine in these nerves. The existence of a functional arginine-citrulline cycle may contribute to a constant supply of L-arginine and suggests a neuronal source of NO for inducing cerebral vasodilation.
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PMID:Arginine synthesis from citrulline in perivascular nerves of cerebral artery. 775 95

Ammonia (NH4OH) generated by urease from urea in the Helicobacter pylori (Hp)-infected stomach is considered as a one of the major pathogenic factors in the Hp-associated gastritis but the mechanism of the deleterious action of NH4OH on gastric mucosa has not been fully explained. In this study, the gastric mucosa was exposed to topical NH4OH in various concentrations (15-250 mM) (series A) and to NH4OH in a small concentration followed by a high concentration (250 mM) of NH4OH (series B) or to the combination of urea and urease to generate NH4OH (series C) followed by 250 mM NH4OH in order to determine the "mild irritant" and protective properties of this substance on the mucosa. Administration of NH4OH alone resulted in a concentration-dependent mucosal damage starting at 30 mM and reaching at 250 mM the degree similar to that obtained with 100% ethanol. The acute mucosal damage by NH4OH was accompanied by the fall in gastric blood flow reaching nadir at 250 mM NH4OH of about 30% of the normal value. When the mucosa was first exposed to low concentration of NH4OH (15 mM) and then insulted with its larger concentration (250 mM), the lesion area was markedly reduced as compared to that obtained with 250 mM NH4OH alone and this effect was accompanied by a significant rise in the GBF. This adaptive cytoprotection by 15 mM NH4OH was reversed, in part, by the pretreatment with indomethacin to inhibit prostaglandins (PG) or L-NAME to suppress nitric oxide (NO) formation or after capsaicin-induced denervation of sensory nerves. Blockade of endogenous sulfhydryls (SH) by N-ethylmaleimide (NEM) eliminated this adaptive cytoprotection but the suppression of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by alpha-difluoro methylornithine (DFMO) failed to influence the protection and accompanying hyperemia afforded by NH4OH in low concentration. The combination of urea (2%) and urease (100 U), which raised the gastric luminal NH4OH concentration by about 5-folds, also reduced significantly the lesions provoked by 250 mM NH4OH. This protection and accompanying hyperemia induced was significantly attenuated by the pretreatment with indomethacin or hydroxyurea, a potent urease inhibitor. Hydroxyurea abolished completely the rise in luminal NH4OH produced by the combined treatment of urea plus urease. We conclude that 1) NH4OH in high concentration damages the gastric mucosa but when applied at lower concentration or generated in the stomach by urea-urease system, acts as local mild irritant to induce adaptive cytoprotection that probably involves PG, sensory nerves and arginine-NO-pathaway.
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PMID:Urea-urease system in cytoprotection against acute mucosal damage. 877 94

Helicobacter pylori (Hp) is considered as the major pathogen in Hp-associated gastritis but the mechanism of its action has not been fully explained. We investigated both the damaging and protective effects of intragastric (i.g.) application of ammonia (NH4OH) and ammonium ion (NH4Cl), the major products of Hp-derived urease, on the rat stomach with intact and capsaicin-deactivated sensory nerves or suppressed prostaglandin (PG) and nitric oxide (NO) synthesis. NH4OH given i.g. resulted in a concentration-dependent mucosal damage starting at 30 mM and reaching maximum at 250 mM (pH 11), the extent of damage being similar to that obtained with 100% ethanol. NaOH solution (1 mM) at pH 11 given i.g. did not affect mucosal integrity. The damage caused by NH4OH was accompanied by the fall in gastric blood flow (GBF) reaching at 250 mM NH4OH about 30% of the vehicle control value. The NH4OH-induced gastric damage was augmented by capsaicin-induced deactivation of sensory nerves, the suppression of nitric oxide (NO) synthase with L-NAME or the decrease of i.g. acidity by ranitidine. The pretreatment with scavengers of reactive oxidants significantly reduced the area of NH4OH-induced gastric lesions. When the mucosa was first exposed to a low 15-mM concentration of NH4OH and then insulted with large 250 mM NH4OH or with 100% ethanol, the lesion area was markedly reduced as compared to that obtained with 250 mM NH4OH or 100% ethanol alone. This adaptive protection by 'mild' concentration of NH4OH against strong irritants (250 mM NH4OH or 100% ethanol) was reversed, in part, by pretreatment with L-NAME and indomethacin. NH4Cl (60-500 mM) given i.g. alone failed to affect the mucosal integrity but when applied before 100% ethanol it produced a concentration-dependent fall in the mucosal damage by these irritants. We conclude that; (1) ammonia at higher concentrations damages the gastric mucosa, while ammonium ion exerts the protective activity; (2) the ammonia-induced gastric damage may involve the formation of reactive oxidants; (3) ammonia at lower concentration acts like a mild irritant via the activation of sensory nerves, NO-arginine pathway and PG.
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PMID:Gastric mucosal damage and adaptive protection by ammonia and ammonium ion in rats. 891 6

Gastrointestinal degradation of urea might, according to a new hypothesis, have consequences for the regulation of acid-base balance as well as control of breathing during infancy. Thirteen infants were investigated from their first few days of life to the age of 6 months by collecting faecal samples at the age of 3 days, 2, 3, and 6 months, respectively. The faecal microflora was determined after aerobic and anaerobic cultivation and the faecal urease activity was assessed after 36 h aerobic and anaerobic preincubation. The infants were mostly breast fed and had a faecal microflora containing anaerobic bacteria such as Bifidobacteria, Bacterioides and Lactobacilli but also aerobics such as Escherichia coli, Enterococci and sometimes Klebsiella. The faecal pH increased from approximately 5.30 to 5.90, the pH after anaerobic preincubation being on an average 0.2 pH units lower than after aerobic preincubation. Simultaneously the nitric oxide production of the faecal specimens increased approximately 10-fold and the urease activity decreased by a factor of 3 to 5. We also found an inhibitory action of nitrate, nitrite (in mumolar concentration) and nitric oxide (in parts per million concentration) on the faecal urease activity. Hence, the present results warrant further research in order to determine more precisely the action of different concentrations of various nitrous oxides on individual bacterial species, and furthermore, to assay the faecal urease activity in victims of sudden infant death syndrome as well as in infants dead due to other causes.
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PMID:Faecal microflora and urease activity during the first six months of infancy. 905 88

Gastric mucosa is exposed to various aggressive factors such as stress, ulcerogenic drugs including acetyl-salicylic acid(ASA)-like agents, ethanol, bacteria, particularly Helicobacter pylori (Hp), and various endogenous irritants such as acid-pepsin secretion and bile salts. The maintenance of the mucosal barrier depends upon the activation of the pre-epithelial (mucus-alkali secretion), epithelial (surface-active phospholipids and rapid mucosal restitution) and post-epithelial (mucosal microcirculation, sensory nerves and mast cells) components of mucosal defense. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is the first of a new generation of H2-receptor antagonists with both antisecretory and cytoprotective activities. Its inhibitory action is similar to that of ranitidine and approximately tenfold greater than cimetidine, and is accompanied by a small and transient increase in plasma gastrin levels. In contrast to ranitidine and other H2-receptor antagonists, ebrotidine exerts a unique cytoprotection against injury by various ulcerogens such as ethanol, ammonia, lipopolysaccharides (LPS), stress and ASA or acidified taurocholate. The mechanism of this protection by ebrotidine is not clear, but it has been shown to stimulate mucus secretion, to increase the quality of adherent mucus gel and to increase gastric mucosal blood flow (GBF), possibly due to enhanced mucosal formation of prostaglandin E2 (PGE2) and nitric oxide (NO). The cytoprotective effects of ebrotidine were observed in rats and confirmed also in humans with gastric lesions induced by ethanol or ASA. Ebrotidine also exerts anti-Helicobacter pylori (Hp) effects by interfering with surface receptors of epithelial cells and inhibiting urease, protease and lipase activity, and by counteracting the noxious effects of Hp-related substances such as ammonia and lipopoly-saccharides (LPS).
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PMID:Studies on the cytoprotective and antisecretory activity of ebrotidine. A review. 920 69

Helicobacter pylori can produce a persistent infection in the human stomach, where chronic and active inflammation, including the infiltration of phagocytes such as neutrophils and monocytes, is induced. H. pylori may have a defense system against the antimicrobial actions of phagocytes. We studied the defense mechanism of H. pylori against host-derived peroxynitrite (ONOO(-)), a bactericidal metabolite of nitric oxide, focusing on the role of H. pylori urease, which produces CO(2) and NH(3) from urea and is known to be an essential factor for colonization. The viability of H. pylori decreased in a time-dependent manner with continuous exposure to 1 microM ONOO(-), i.e., 0.2% of the initial bacteria remained after a 5-min treatment without urea. The bactericidal action of ONOO(-) against H. pylori was significantly attenuated by the addition of 10 mM urea, the substrate for urease, whereas ONOO(-)-induced killing of a urease-deficient mutant of H. pylori or Campylobacter jejuni, another microaerophilic bacterium lacking urease, was not affected by the addition of urea. Such a protective effect of urea was potentiated by supplementation with exogenous urease, and it was almost completely nullified by 10 microM flurofamide, a specific inhibitor of urease. The bactericidal action of ONOO(-) was also suppressed by the addition of 20 mM NaHCO(3) but not by the addition of 20 mM NH(3). In addition, the nitration of L-tyrosine of H. pylori after treatment with ONOO(-) was significantly reduced by the addition of urea or NaHCO(3), as assessed by high-performance liquid chromatography with electrochemical detection. These results suggest that H. pylori-associated urease functions to produce a potent ONOO(-) scavenger, CO(2)/HCO(3)(-), that defends the bacteria from ONOO(-) cytotoxicity. The protective effect of urease may thus facilitate sustained bacterial colonization in the infected gastric mucosa.
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PMID:Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production. 1089 33

Exposure to unfavorable conditions results in the transformation of Helicobacter pylori, a gastric pathogen, from a bacillary form to a coccoid form. The mechanism and pathophysiological significance of this transformation remain unclear. The generation of the superoxide radical by H. pylori has previously been shown to inhibit the bactericidal action of nitric oxide, the concentration of which is relatively high in gastric juice. With the use of chemiluminescence probes, both the quality and quantity of reactive oxygen species generated by H. pylori have now been shown to change markedly during the transformation from the bacillary form to the coccoid form. The transformation of H. pylori was associated with oxidative modification of cellular proteins, including urease, an enzyme required for the survival of this bacterium in acidic gastric juice. Although the cellular abundance of urease protein increased during the transformation, the specific activity of the enzyme decreased and it underwent aggregation. Specific activities of both superoxide dismutase and catalase in H. pylori also decreased markedly during the transformation. The transformation of H. pylori was also associated with oxidative modification of DNA, as revealed by the generation of 8-hydroxyguanine, and subsequent DNA fragment. These observations indicate that oxidative stress elicited by endogenously generated reactive oxygen species might play an important role in the transformation of H. pylori from the bacillary form to the coccoid form.
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PMID:Oxidative cellular damage associated with transformation of Helicobacter pylori from a bacillary to a coccoid form. 1093 57

H. pylori colonisation of the stomach causes the recruitment of the inflammatory cells by the adherence of the bacteria with the epithelium and the release of factors of virulence either to the contact (oipA or other soluble factors) or in the cell by translocation (CagA). Such contact triggers interleukin 8 expression in the epithelial cell and attracts lymphocytes and monocytes into the chorion. Bacterial lipopolysaccharide and urease support the activation of these inflammatory cells. The lymphocytes produce pro-inflammatory cytokines, which direct the immune response towards the Th1 pathway. The variability of the inflammatory response depends on hereditary factors of the host such as the interleukin 1 genotypes, which determine the level of the pro-inflammatory cytokine expression, and of bacterial factors such as the cag pathogenicity island, the lipopolysaccharide and the vacuolating toxin, vacA. The mucosal inflammation provokes apoptosis and atrophy of the epithelial cells through the effect of pro-inflammatory cytokines and free radicals. Epithelial proliferation is a consequence of excessive apoptosis caused by the infection. It is stimulated by the expression of inducible cyclo-oxygenase and inducible nitric oxide synthase. The development of atrophic gastritis towards cancer is supported by nitric oxide which has a mutagenic effect on DNA and inhibits p53 protein and by the bacterium itself which decreases DNA mismatch repairing activity. The gastritis induced by Helicobacter pylori changes acid secretion according to the prevalent location of the gastritis in the antrum or in the gastric body. Prevalent gastritis in the gastric body causes hypochlorhydria by reducing the release of histamin from ECL cells and inhibiting the parietal cells through the effect of tumor necrosis factor and interleukin 1-beta. Hypochlorhydria is more marked among patients having a pro-inflammatory genotype for interleukin 1-beta and those infected by bacteria with virulence factors. In the event of antrum predominant gastritis, the pro-inflammatory cytokines cause a reduction of somatostatin and gastrin releases from the D and the G cells, respectively. The result of all is increased maximal acid output and the meal-stimulated acid secretion.
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PMID:[What are the gastric modifications induced by acute and chronic Helicobacter pylori infection?]. 1270 Apr 95

Although it has been shown that hydroxyurea (HU) therapy produces measurable amounts of nitric oxide (NO) metabolites, including iron nitrosyl hemoglobin (HbNO) in patients with sickle cell disease, the in vivo mechanism for formation of these is not known. Much in vitro data and some in vivo data indicates that HU is the NO donor, but other studies suggest a role for nitric oxide synthase (NOS). In this study, we confirm that the NO-forming reactions of HU with hemoglobin (Hb) or other blood constituents is too slow to account for NO production measured in vivo. We hypothesize that, in vivo, HU is partially metabolized to hydroxylamine (HA), which quickly reacts with Hb to form methemoglobin (metHb) and HbNO. We show that addition of urease, which converts HU to HA, to a mixture of blood and HU, greatly enhances HbNO formation.
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PMID:Urease enhances the formation of iron nitrosyl hemoglobin in the presence of hydroxyurea. 1288 Sep 48

This review covers progress in identifying Helicobacter pylori-derived factors that are involved in survival and virulence of the organism and in elucidating host response pathways that can limit the infection but are also susceptible to dysregulation. Recent work has identified genes of the cytotoxin-associated gene (cag) pathogenicity island (PAI) involved in regulating signaling, interleukin-8 secretion, and phenotypic events in epithelial cells. New roles in pathogenesis have been recognized for vacuolating toxin A (VacA) and urease, H. pylori membrane and secreted factors, and host epithelial surface molecules. Molecular pathways involved in H. pylori-induced apoptosis in epithelial cells, T cells, and macrophages are being dissected. Activation of toll-like receptors and bacterial factors involved in nitric oxide (NO) and reactive oxygen species induction were also described. The ability of H. pylori to limit NO production by several mechanisms may be an important part of its ability to evade the host immune response.
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PMID:Helicobacter pylori infection: pathogenesis. 1569 86


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