Pw Bliss

How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology.

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.

Gastrointestinal responses to a panel of lectins in rats maintained on total parenteral nutrition.

Total parenteral nutrition (TPN) causes atrophy of gastrointestinal epithelia, so we asked whether lectins that stimulate epithelial proliferation can reverse this effect of TPN. Two lectins stimulate pancreatic proliferation by releasing CCK, so we asked whether lectins that stimulate gastrointestinal proliferation also release hormones that might mediate their effects. Six rats per group received continuous infusion of TPN and a once daily bolus dose of purified lectin (25 mg ⋅ rat-1 ⋅ day-1) or vehicle alone (control group) for 4 days via an intragastric cannula. Proliferation rates were estimated by metaphase arrest, and hormones were measured by RIAs. Phytohemagglutinin (PHA) increased proliferation by 90% in the gastric fundus ( P < 0.05), doubled proliferation in the small intestine ( P < 0.001), and had a small effect in the midcolon ( P< 0.05). Peanut agglutinin (PNA) had a minor trophic effect in the proximal small intestine ( P < 0.05) and increased proliferation by 166% in the proximal colon ( P < 0.001) and by 40% in the midcolon ( P < 0.001). PNA elevated circulating gastrin and CCK by 97 ( P< 0.05) and 81% ( P < 0.01), respectively, and PHA elevated plasma enteroglucagon by 69% and CCK by 60% (both P < 0.05). Only wheat germ agglutinin increased the release of glucagon-like peptide-1 by 100% ( P < 0.05). PHA and PNA consistently reverse the fall in gastrointestinal and pancreatic growth associated with TPN in rats. Both lectins stimulated the release of specific hormones that may have been responsible for the trophic effects. It is suggested that lectins could be used to prevent gastrointestinal atrophy during TPN. Their hormone-releasing effects might be involved.

Nα-Methylhistamine: association with Helicobacter pylori infection in humans and effects on gastric acid secretion

Infection with the bacterium Helicobacter pylori is associated with altered gastric acid secretion and gastrointestinal disease. Recent work has suggested that Nα-methylhistamine, produced by the bacterium and acting on histamine receptors in gastric tissue, might be involved. Gastric juice and tissue biopsies from infected patients have been analysed for the presence of Nα-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry. Nα-Methylhistamine was detected in five of seven samples of gastric juice from infected patients (5–180 pmol/ml) but was absent in nine uninfected subjects. The compound was not found in fundic and antral biopsies from both subject groups. Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of Nα-methylhistamine. Instillation of this compound at 10−5 mol/l into the gastric lumen produced a significant increase in acid secretion in vivo while plasma gastrin concentration remained unchanged. Nα-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium. The concentrations found are below those required to affect acid secretion or gastrin production in vivo, although higher local concentrations may exist around a site of infection.

EFFECT OF PACAP-27 ON 14C-AMINOPYRINE ACCUMULATION IN ISOLATED RABBIT PARIETAL CELLS

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in gastric mucosa, but its direct effect on parietal cells is unknown. We examined this using 14C-aminopyrine uptake in elutriated rabbit cells. PACAP-27 had no effect on basal cells but significantly increased the response to histamine (10(-4) M) at 10(-9) M and to carbachol (10(-4) M) in the presence of ranitidine (10(-4) M) at 10(-7) M and 10(-8) M. PACAP (6-38), an antagonist of PACAP, inhibited the effect of PACAP-27 on carbachol-stimulated cells. Vasoactive intestinal peptide had no significant effect. In conclusion, PACAP-27 has a direct additive effect on stimulated rabbit parietal cells in vitro.

Analysis of Nα-methylhistamine by gas chromatography–mass spectrometry

A gas chromatography–electron capture mass spectrometry assay has been developed for the histamine H3 receptor agonist, Nα-methylhistamine (Nα-MH). The assay is linear from 50 pg–10 ng, with a limit of detection of 50 pg/ml for gastric juice and plasma, and 50 pg/sample for bacteria (107–108 CFU) and gastric tissue (5–10 mg wet weight). The limits of quantification are 100 pg/ml for gastric juice (%RSD=1.4) and plasma (%RSD=9.4), and 100 pg/sample for bacteria (%RSD=3.9) and tissue (%RSD=5.8). Nα-MH was not present in human plasma, but low levels (1.4 ng/ml and 0.4 ng/ml) were detected in two samples of human gastric juice obtained from patients infected with Helicobacter pylori.