Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urease and ammonia (NH4OH) have been proposed to be play a major role in the pathogenesis of the the Helicobacter pylori (Hp)-associated gastric damage but the mechanism of this damage has not been fully explained. This study was designed the determine whether topical application with NH4OH at low concentration or the generation of the NH4OH in gastric lumen by the hydrolysis of urea in the presence of urease can induce adaptive cytoprotection. Single insult of NH4OH alone in various concentrations (15-500 mM) caused the mucosal damage starting at 30 mM and reaching at 250 mM the value similar to that obtained with 100% ethanol and being accompanied by the fall in gastric blood flow to about 30% of the normal value. When the mucosa was first exposed to the low concentration (15 mM) of NH4OH, causing by itself only small microscopic damage of surface epithelium, but then insulted by a high concentration (250 mM) of NH4OH, the extent of mucosal damage was greatly attenuated as compared to that caused by NH4OH alone. This "adaptive" cytoprotection, accompanied by the rise in the GBF, was reversed in part, after the pretreatment with indomethacin to inhibit PG-cyclooxygenase, with L-NAME to suppress NO-synthase or with capsaicin to induce deactivation of sensory nerves. The combined topical pretreatment with urea (2%) and urease (100 U) to generate NH4OH in the stomach, also significantly reduced the severity of gastric lesions induced by 100% ethanol and this was also accompanied by a significant rise in the gastric blood flow. The protective and hyperemic effects of urea and urease were significantly attenuated by the pretreatment with indomethacin or suppression of NO-synthase by L-NAME. The functional ablation of sensory nerves by the pretreatment with capsaicin also reversed, in part, the protective effect of the combination of urea plus urease and abolished completely the mucosal hyperemia accompanying this protection. We conclude that 1) NH4OH alone at higher concentrations damages the gastric mucosa but when applied at lower concentration corresponding to that in the stomach of Hp-infected patients, or generated by the urea in the presence of urease, NH4OH acts like "mild irritant" to induce adaptive cytoprotection, 2) this adaptive cytoprotection is mediated, in part, by endogenous PG, sensory nerves and arginine-NO-dependent pathway.
 ...
PMID:Adaptive cytoprotection by ammonia and urea-urease system in the rat gastric mucosa. 877 Jul 91

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.
 ...
PMID:Urea-urease system in cytoprotection against acute mucosal damage. 877 94