Effect of ammonia on the gastric mucosa in rats: Pathophysiological importance of urease in gastric ulcer disease.

Murakami, Motonobu; Yoo, Jung Keun; Inada, Masami; Miyake, Teruki

doi:10.1254/jjp.47.330

Cited by 25 publications

(8 citation statements)

References 7 publications

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“…33 The increase in serum pepsinogen I was particularly marked in the renal failure patients with H pylon, with its concentration being double that in the renal patients without the infection. It has previously been reported that H pylon infection raises serum pepsinogen I in non-uraemic patients but only by about 25%.7 3 The fact that H pylon infection raises serum pepsinogen I to a greater extent in uraemic than non-uraemic subjects would be consistent with bacterial ammonia production raising the serum concentration of the zymogen. However, little is known about the mechanism by which pepsinogen I reaches the serum or about the mechanism of its renal excretion.33 If it is excreted by a saturable process then in patients with renal failure the same degree of increased delivery of pepsinogen I into the serum could produce a more marked increase in its serum concentration.…”

Section: Discussionmentioning

confidence: 80%

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Nujumi

Rowe

Dahill

et al. 1992

Gut

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Studies were performed in patients with and without renal failure to investigate the role of bacterial ammonia production in the pathogenesis of the mucosal abnormalities caused by Helicobacter pylori. The high rate of H pylon ammonia production in uraemic patients should accentuate any ammonia induced effects. The median (range) gastric juice ammonium concentration in the H pylori positive patients with renal failure was 19 mmol/l (1I-43) compared with 5 mmoIl (1-11) in the H pylon positive patients without renal failure (p<0005). In the H pylori negative patients the values were 3 mmol/l (0.5-11) and 0.7 mmol/l (0.1-1.4) respectively in the patients with and without renal failure (p

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Section: Discussionmentioning

confidence: 80%

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Nujumi

Rowe

Dahill

et al. 1992

Gut

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“…Recently, the role of ammonia in H. pv/or/'-related gas tric mucosal damage has been widely recognized, and its toxic effect on normal gastroduodenal mucosa is well doc umented [10,11,[13][14][15][16][17], Nevertheless, most previous studies revealed the influences of ammonia only on the epithelium or gastric mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…It is now widely accepted that Helicobacter pylori is related to gastroduodenal diseases [8][9][10][11][12], The effect of ammonia, which is produced by the urease activity of H. pylori, on normal gastric mucosa has been well docu mented [13][14][15][16][17], Although a few papers refer to the effects of ammonia on gastric ulcer healing, those on the collagen metabolism in the ulcer base remain totally unclear.…”

Section: Introductionmentioning

confidence: 99%

Effects of Intragastric Ammonia on Collagen Metabolism of Gastric Ulcer Base in Rats

Endô

Tsukamoto²,

Arisawa³

et al. 1996

Digestion

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We studied the chronic effect of ammonia, which is one of the pathogenic factors of Helicobacter pylori in gastroduodenal diseases, on the healing of acetic acid-induced gastric ulcers in rats with special reference to the collagen metabolism. Rats were given either tap water or 0.1 or 0.02% ammonia solution before and after ulcer induction. We measured the ulcer index, hydroxy-proline concentrations and type III collagen/total hydroxyproline ratios in the ulcer base. Epithelialization was achieved 4 weeks later under the influence of ammonia. Nevertheless, ammonia treatment significantly increased the collagen deposition in the ulcer base compared with the nonammonia treatment group, 4 weeks after ulcer induction. In the nonammonia treatment group, the type III collagen/total hydroxyproline ratio decreased 3 weeks after ulcer induction. On the contrary, in the groups treated with ammonia throughout the experiment, type III collagen/total hydroxyproline ratio remained high until 4 weeks after ulcer induction. In conclusion, intragastric ammonia delayed the ulcer healing process in its early phase, but did not affect the achievement of re-epithelialization. However, it disturbed the collagen metabolism in the ulcer base. Excessive deposition of collagen and an abnormally high proportion of its immature type may be unfavorable for ulcer healing. These findings may explain in part why H. pylori-màuccå ulcer is so difficult to treat.

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“…Ammonia is produced by the urease of Helicobacter pylori in the gastric mucosa, and it is considered to be one of the pathogens for H. pylori-induced gastric mucosal injury. NH 3 -AGML was first described by Murakami et al (1988a). It was reported to be inhibited by antioxidative agents (Murakami et al, 1989) and not by prostaglandins (PGs) (Murakami et al, 1988b).…”

Section: Antisecretory and Antiulcer Effects Of Cs-526 315mentioning

confidence: 99%

Pharmacological Profile of Novel Acid Pump Antagonist 7-(4-Fluorobenzyloxy)-2,3-dimethyl-1-{[(1 S,2 S)-2-methyl cyclopropyl]methyl}-1 H-pyrrolo[2,3-d]pyridazine (CS-526)

Ito¹,

Kinoshita²,

Tomizawa³

et al. 2007

The Journal of Pharmacology and Experimental Therapeutics

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The pharmacological profiles of the novel acid pump antagonist 7-(4-fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methylcyclopropyl]methyl}-1H-pyrrolo[2,3-d]pyridazine (CS-526) were investigated in terms of hog gastric H ϩ ,K ϩ -ATPase activity, gastric acid secretion, and acute gastroesophageal lesions in comparison with other proton pump inhibitors (PPIs). CS-526 inhibited H ϩ ,K ϩ -ATPase activity in a concentration-dependent manner, with an IC 50 value of 61 nM. The inhibitory effect of CS-526 on H ϩ ,K ϩ -ATPase activity was more potent than that of any of the other PPIs examined. The inhibitory mechanism of CS-526 on H ϩ ,K ϩ -ATPase was a competitive antagonism to the K ϩ binding site of H ϩ ,K ϩ -ATPase, and it was also a reversible inhibition. In pylorus-ligated rats, intraduodenal or oral administration of CS-526 inhibited gastric acid secretion in a dose-dependent manner, and the ID 50 values were 2.8 or 0.7 mg/kg, respectively. In Heidenhain pouch dogs, intrapouch administration of CS-526 inhibited histamine-stimulated gastric acid secretion in a dose-and retention time-dependent manner. In a reflux esophagitis model, intraduodenal and oral administration of CS-526 prevented esophageal lesions with ID 50 values of 5.4 and 1.9 mg/kg, respectively. Lansoprazole prevented esophagitis only by intraduodenal administration (ID 50 ϭ 2.2 mg/kg). Furthermore, CS-526 inhibited acute gastric mucosal lesions. These data demonstrate that the novel acid pump antagonist CS-526 has potent antisecretory and antiulcer effects. These findings indicate that CS-526 would have a curative effect on gastroesophageal reflux disease via its potent antisecretory and antiulcer actions.

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Effect of ammonia on the gastric mucosa in rats: Pathophysiological importance of urease in gastric ulcer disease.

Cited by 25 publications

References 7 publications

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Effects of Intragastric Ammonia on Collagen Metabolism of Gastric Ulcer Base in Rats

Pharmacological Profile of Novel Acid Pump Antagonist 7-(4-Fluorobenzyloxy)-2,3-dimethyl-1-{[(1 S,2 S)-2-methyl cyclopropyl]methyl}-1 H-pyrrolo[2,3-d]pyridazine (CS-526)

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