Role of luminal ammonia in the development of gastropathy and hypergastrinemia in the rat

Lichtenberger, Lenard M.; Dial, Elizabeth J.; Romero, Jimmy J.; Lechago, Juan; Jarboe, Linda A.; Wolfe, M. Michael

doi:10.1016/0016-5085(95)90056-x

Cited by 47 publications

(25 citation statements)

References 34 publications

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“…Decreased inhibition of gastrin release by somatostatin, with resultant hypergastrinemia and increased parietal cell mass, has been postulated as the cause of hyperacidity and duodenal ulceration (48,58). Decreased mucosal somatostatin and increased gastrin may be a consequence of antral inflammation or perhaps chronic ammonia exposure (10,40). The proinflammatory cytokines IL-1␤ and TNF-␣, which are expressed in H. pylori-infected people (41,50,72), inhibit somatostatin release (3) and stimulate gastrin release (1,2,39) by antral G cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter felisInfection Is Associated with Lymphoid Follicular Hyperplasia and Mild Gastritis but Normal Gastric Secretory Function in Cats

et al. 2000

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The relationship of Helicobacter felis, a bacterium observed in the stomachs of cats, to gastric disease is unclear. The objective of this study was to determine if H. felis infection alters gastric histopathology, proinflammatory cytokine expression, and secretory function and evokes a humoral immune response in cats. Five specific-pathogen-free (SPF) Helicobacter-free cats were studied before and for 1 year after oral inoculation with H. felis (ATCC 49179). Four SPF H. felis-uninfected cats served as controls. The stomachs of all five H. felis-inoculated cats became colonized, as determined by urease activity, histopathology, PCR, culture, and transmission electron microscopy of serial gastric biopsies at 0, 3, 5, 8, and 12 months. Uninoculated cats remained Helicobacter free. Lymphoid follicular hyperplasia, atrophy, and fibrosis were observed primarily in the pylorus of infected cats. Mild mononuclear inflammation was detected in both infected and uninfected cats, but was more extensive in infected cats, with pangastric inflammation, eosinophilic infiltrates, and cardia gastritis observed only in infected cats. No upregulation of antral mucosal interleukin 1␣ (IL-1␣), IL-1␤, or tumor necrosis factor alpha was detected by reverse transcription-PCR in any cat. The gastric secretory axes, assessed by fasting plasma gastrin, antral mucosal gastrin and somatostatin immunoreactivity, and pentagastrin-stimulated gastric acid secretion, were similar in both infected and uninfected cats. Gradual seroconversion (immunoglobulin G) was observed in four of five infected cats, with enzyme-linked immunosorbent assay values reaching 4؋ to 12؋ baseline 12 months postinfection. These findings indicate that H. felis infection in cats induces lymphoid follicular hyperplasia, mild gastritis, and seroconversion, but is associated with normal gastric secretory function.

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Section: Discussionmentioning

confidence: 99%

Helicobacter felisInfection Is Associated with Lymphoid Follicular Hyperplasia and Mild Gastritis but Normal Gastric Secretory Function in Cats

et al. 2000

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“…It has been suggested that the facilitated gastrin release in Hp - infected patients may be the result of a reduced or blocked release of antral somatostatin, but the underlying mechanism has not been explained [42]. Hypergastrinemia, observed in Hp -infected mucosa, was attributed to either inflammatory cytokines [43]and/or alkalinization of the antral part of the stomach due to the local rise in antral pH by prolonged elevation of ammonia in the gastric juice caused by the urease activity of Hp [44, 45]. It is not excluded that the impairment in the gastrin-somatostatin link observed in our present study is mediated by upregulated expression of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Water Extracts of <i>Helicobacter pylori</i> Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link

Brzozowski

Konturek

et al. 1999

Digestion

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Background: Helicobacter pylori (Hp) is considered as a major risk factor of peptic ulcer, but the pathogenic mechanism of its action has not been fully explained. Aims: This study was designed: (1) to compare the ulcer healing effects of water extract (WE) obtained from type-I cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) expressing Hp and from type-II CagA- and VacA-negative Hp strain with those of vehicle (saline), and (2) to determine the alterations in gastric secretion, gastric blood flow (GBF) and expression of Hp-related cytokines during the ulcer healing in rats treated with toxigenic (type-I) and non-toxigenic (type-II) Hp-derived WE. Methods: Gastric ulcers were produced by serosal application of acetic acid in rats with or without gastric fistula treated with vehicle (saline) or WE originating from type-I or type-II Hp administered intragastrically on days 1, 3, 5 and 7 upon ulcer induction. On days 3, 9 and 15, animals were lightly anesthetized with ether, the abdomen was opened and the GBF was measured by the H₂-gas clearance technique in the ulcer area and non-ulcerated mucosa. Venous blood was withdrawn for the measurement of plasma cytokine (IL-1β and TNFα) levels and plasma and gastric contents were also collected for gastrin and somatostatin determination by specific radioimmunoassay. Results: Gastric ulcers healed gradually in vehicle-treated controls and the ulcer area on days 3, 9 and 15 was reduced by 12, 43 and 92%, respectively. In rats treated with WE of type-I Hp, ulcer healing was significantly delayed, and gastritis and infiltration of ulcerated gastric mucosa with inflammatory cells were observed histologically. The prolongation of ulcer healing by WE of both Hp strains was accompanied by a marked fall in the GBF at the ulcer margin and transient hyposecretion especially in rats given WE of type-I Hp strain. On day 15 of ulcer healing, the plasma concentration of IL-1β and TNFα was negligible in vehicle control rats, but it was significantly elevated particularly in rats treated with WE of type-I Hp. RT-PCR analysis revealed that mucosal expression of IL-1β and TNFα mRNA was significantly upregulated in the gastric mucosa of rats treated with either toxigenic or non-toxigenic Hp WE. The plasma gastrin level was significantly higher and the luminal concentration of somatostatin was significantly lower in rats treated with Hp-WE than in vehicle-treated controls and these alterations were more pronounced in rats treated with WE type-I than type-II Hp. Conclusions: WE of toxigenic Hp strain delays ulcer healing due to the reduction in the gastric microcirculation at the ulcer margin, the overexpression of inflammatory cytokines and the impairment of the gastrin-somatostatin link.

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“…On the contrary, complete urease inhibition does not result in a decrease of gastrin secretion [28, 29]. However, it has been noted that long-term exposure to ammonia leads to hypergastrinemia [30]. An alternative potential mechanism might be the production of gastrin-stimulating cytokines such as interleukin-1β and tumor necrosis factor-α from T lymphocytes and monocytes present in the inflammatory infiltrate engendered by H. pylori [31, 32].…”

Section: Biochemical Characteristics Of Gastrinmentioning

confidence: 99%

Gastrin and the Enterochromaffin-Like Cell: An Acid Update

Kidd

Modlin²,

Tang³

1998

Dig Surg

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Gastrin is synthesized and secreted mostly in a heptadecapeptide form from neurocrine G cells located in the antrum. The biologically active sequence of the molecule is a C-terminal pentapeptide, which has been conserved across many species. Transcriptional regulation of gastrin mRNA synthesis is positively regulated by transforming growth factor-α (TGF-α) and inhibited by somatostatin (SST). The inactive precursor form is converted to the active molecule by several posttranslation processing steps which include cleavage, C-terminal amidation, glycosylation, phosphorylation and sulfation. Aberrations in processing steps generate incompletely processed forms, particularly glycosylated progastrin, which may act as autocrine growth factors for gastrointestinal neoplasms. Gastrin release is stimulated by luminal aromatic amino acids and inhibited by a decrease in luminal pH. Other gastrin agonists include β-adrenergic agents, acetylcholine, gastrin-releasing peptide (bombesin), TGF-α, and possibly the gastric pathogen, Helicobacter pylori. The principal peptide inhibitor of gastrin release is SST. The major physiological roles of gastrin include stimulation of acid secretion, regulation of mucosal cell lineage and mucosal cell proliferation. The fundic enterochromaffin-like (ECL) cell is the principal cellular transducer of the gastrin-acid signal. Activation of its gastrin/CCK_B receptor results in histamine synthesis and release with consequent activation of the fundic parietal cell H₂ receptor. An increase in luminal pH caused by acid inhibitory pharmacotherapy agents (particularly proton pump inhibitors) results in hypergastrinemia and ECL cell hyperplasia. Gastric carcinoids however appear occur in patients with multiple endocrine neoplasia type I syndrome, suggesting that an associated genomic defect is necessary. Gastrin is thus both a potent gastrointestinal trophic and histamine secretory agent. As a hormone it is a paradigm in the elucidation of both cellular secretory and growth factor induced cell proliferation.

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Role of luminal ammonia in the development of gastropathy and hypergastrinemia in the rat

Cited by 47 publications

References 34 publications

Helicobacter felisInfection Is Associated with Lymphoid Follicular Hyperplasia and Mild Gastritis but Normal Gastric Secretory Function in Cats

Helicobacter felisInfection Is Associated with Lymphoid Follicular Hyperplasia and Mild Gastritis but Normal Gastric Secretory Function in Cats

Water Extracts of <i>Helicobacter pylori</i> Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link

Gastrin and the Enterochromaffin-Like Cell: An Acid Update

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