Lipopolysaccharide-induced inhibition of gastric acid and pepsin secretion in rats

Uehara, Akira; Okumura, Toshikatsu; Okamura, Kiyoshi; Takasugi, Yuichi; Namiki, Masayoshi

doi:10.1016/0014-2999(90)90256-6

Cited by 22 publications

(11 citation statements)

References 5 publications

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“…Our results with antisecretory effects of Hp-LPS and other non-Hp-related LPSs agree with those of Uehara et al (1990) and Konturek et al (2001) that show that peripheral and central applications of LPS derived from E. coli to rats produces profound dose-dependent inhibition of gastric acid output. Since ASA damage depends upon gastric acidity, it is reasonable to assume that suppression of gastric acid secretion by this endotoxin could contribute to the limitation of this damage.…”

Section: Discussionsupporting

confidence: 92%

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2004

J Pharmacol Exp Ther

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Lipopolysaccharide (LPS) is one of the virulence factors in theHelicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASAinduced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1␤, and tumor necrosis factor-␣ levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK 2 ) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido}-3 phenyl}-2 propronique] but not by loxiglumide, an antagonist of CCK 1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK 2 /gastrin receptors.Helicobacter pylori (Hp) is now generally accepted as a major cause of chronic gastritis and an important risk factor for peptic ulcer disease and gastric cancer (Warren and Marshall, 1983;Konturek et al., 1999), but it remains unknown whether the gastric mucosa is capable of adapting to repeated Hp insults and whether such Hp adaptation might alter the mucosal resistance to the injurious action of strong irritants.Various pathogenic factors originating from Hp have been implicated in the damaging effect of this bacterium on the gastric mucosa, the most important in addition to ammonia being cytotoxins released by Hp strains expressing the vacuolating cytotoxin A and cytotoxin-associated gene A proteins, Hp-derived lipopolysaccharides (Hp-LPSs), and the enhanced generation of reactive oxygen species (Megraud et al., 1992;Crabtree, 1996;Figura and Tabaqchali, 1996; Moran, 2001a,b). Hp-LPS exhibits a low immunological activity, and this property has been assumed to play an important role in the persistency of Hp infection in the human stomach (Moran, 2001a,b). Nevertheless, the deleterious action of LPS derived from Hp in the stomach includes an interaction of this endotoxin with laminin (Valkonen et al., 1994), its influe...

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Section: Discussionsupporting

confidence: 92%

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2004

J Pharmacol Exp Ther

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“…This effect may be due to an inhibition of gastric acid secretion and hypergastrinemia, known to exert a trophic influence on the gastric mucosa [43]. Since, as shown before [12, 14, 44, 45], parenteral HP LPS exhibits antisecretory action and hypergastrinemia, it is likely that these effects may also contribute significantly to the enhanced resistance of the gastric mucosa to repeated insults with this endotoxin observed in our present study.…”

Section: Discussionmentioning

confidence: 53%

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to <i>Helicobacter pylori</i> Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2003

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Background and Aim: Lipopolysaccharide (LPS) has been proposed to act as one of numerous virulence factors in the Helicobacter pylori (HP)-infected stomach. However, little is known as to whether the gastric mucosa can withstand the repeated LPS insult, and how the possible adaptation to this endotoxin influences the damage induced by strong irritants. We determined the effect of a single or repeated parenteral administration of LPS obtained from HP on acute gastric lesions induced by intragastric application of 100% ethanol (1.5 ml) and by water immersion and restraint stress (WRS). Methods: The area of the gastric lesions was measured by planimetry, mucosal gastric blood flow (GBF) was determined by H₂ gas clearance, and gastric luminal content was collected for the determination of luminal NO₂^–/NO₃^– levels by the Griess reaction. Biopsy samples were taken for the measurement of prostaglandin (PG) E₂ by radioimmunoassay and mucosal expression of constitutive and inducible nitric oxide synthase (cNOS and iNOS), constitutive (COX-1) and inducible cyclooxygenase (COX-2), heat shock protein 70 (HSP 70) mRNA and protein were analyzed by RT-PCR and Western blot. Results:HP LPS (1 mg/kg i.p.) injected once or 5 times produced negligible macroscopic injury and failed to influence GBF significantly compared to the injuries recorded in vehicle-controlled rats. Single and repeated (5 times) administration of HP LPS significantly reduced ethanol- and WRS-induced lesions, these protective effects were accompanied by a rise in GBF and excessive luminal release of NO. The suppression of NOS activity by L-NAME (20 mg/kg i.p.), a nonspecific NOS inhibitor, or L- (30 mg/kg i.g.), a specific iNOS inhibitor, and of COX-2 activity by NS-398 reversed the protective and hyperemic effects of single or repeated LPS administrations against ethanol and WRS damage and the accompanying rise in NO and PGE₂ production. These effects of L-NAME were significantly antagonized by the addition of L-arginine, a substrate for NO synthesis. The signals for cNOS, COX-1 and HSP 70 mRNA were detected by RT-PCR in the vehicle-treated gastric mucosa, whereas gene and protein expression of iNOS, COX-2 and HSP 70 mRNA were significantly increased only in rats treated with 1 or 5 applications of HP LPS. Conclusions: Repeated injections of HP LPS enhance gastric mucosal resistance to the mucosal damage induced by ethanol and WRS via a mechanism involving mucosal overexpression of iNOS, COX-2 and HSP 70 with subsequent excessive production of NO and PGE₂.

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“…In particular, these reports focused on the effect of E. coli-derived LPS, and its in vivo inhibitory effect has remained undisputed. Also, E. coliderived LPS was shown to exert a lasting inhibitory effect on pepsinogen secretion (28). However, subsequent research revealed that the observed effect was reversible (29) and that the inhibitory effect of LPS from E. coli may have been caused by the involvement of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 93%

“…In the present study, only LPS of the Sydney strain of H. pylori caused direct stimulation of acid secretion, whereas the other tested preparations did not cause any significant change in acid secretion. A number of earlier reports have shown that LPS from gram-negative bacteria was able to inhibit acid secretion in vivo (1,28,32). In particular, these reports focused on the effect of E. coli-derived LPS, and its in vivo inhibitory effect has remained undisputed.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of Helicobacter infection can modulate acid secretion by altering the physiology of G cells, D cells, and parietal cells (7). It can do this either by the direct presence of its metabolites or through induction of the inflammatory process as mediated by a wide range of cytokines.Gram-negative bacterial lipopolysaccharide (LPS) from a number of bacterial species effectively inhibits gastric acid secretion in vivo (1,6,26,28,32). However, the mechanism of LPS action suggests the involvement of inflammatory products or mediators such as cytokines and prostaglandins (25,27).…”

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confidence: 99%

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Effect of Purified Lipopolysaccharides from Strains of Helicobacter pylori and Helicobacter felis on Acid Secretion in Mouse Gastric Glands In Vitro

2001

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As a bacterial product, Helicobacter pylori lipopolysaccharide (LPS) can originate in close proximity to parietal cells, but the role of this uniquely structured endotoxin on acid secretion has not been fully investigated and remains unclear. The purpose of this study was to test the direct effect of purified LPS (tested range, 0.1 to 100 g/ml) from various strains of H. pylori and from one Helicobacter felis strain on histamine-and carbachol-stimulated acid secretion in vitro using mouse gastric glands and the accumulation of [ 14 C]aminopyrine. In addition, we investigated whether H. pylori LPS can interfere with two native antisecretory substances, prostaglandin E 2 (PGE 2 ) and somatostatin, which may contribute to bacterial pathogenicity. Except for the LPS from H. pylori SS1 (Sydney strain), which gave a statistically significant increase in both histamine-and carbachol-stimulated acid output (38 and 24%, respectively; P < 0.05), no effect of the tested LPS was observed on acid secretion. H. pylori LPS purified from a patient isolate did not affect the potency or the efficacy of the inhibitory dose response curve to PGE 2 or somatostatin. Bacterial interstrain variation in the direct stimulatory effect of Helicobacter-derived LPS on acid secretion was observed, which probably reflects the molecular structure of LPS and the potential to contribute to virulence. Importantly, the data showed that H. pylori LPS did not have any direct antisecretory properties. It can be speculated that the acid stimulatory properties of LPS from H. pylori SS1 may contribute to the gastric damage observed in the mouse model of H. pylori infection.Helicobacter spp. are known to colonize the stomach of mice with the subsequent development of gastritis. This has led to the development and standardization of a mouse model of Helicobacter pylori-induced gastritis (15). Both bacterial factors and host resistance contribute to the severity of H. pyloriinduced pathology (5). Gastric acid secretion can be beneficial while it acts as a part of the host defense mechanism preventing bacterial infection and hence pathogenicity. However, it also leads to erosive ulcers of the stomach and/or duodenum. Consequently, it also plays a key role in the colonization patterns of Helicobacter species, as increased acid secretion tends to keep bacterial colonization in the antral region of the stomach whereas decreased acid secretion permits bacterial colonization and spread throughout the corpus (14, 30). The presence of Helicobacter infection can modulate acid secretion by altering the physiology of G cells, D cells, and parietal cells (7). It can do this either by the direct presence of its metabolites or through induction of the inflammatory process as mediated by a wide range of cytokines.Gram-negative bacterial lipopolysaccharide (LPS) from a number of bacterial species effectively inhibits gastric acid secretion in vivo (1,6,26,28,32). However, the mechanism of LPS action suggests the involvement of inflammatory products or mediators such as cyt...

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Lipopolysaccharide-induced inhibition of gastric acid and pepsin secretion in rats

Cited by 22 publications

References 5 publications

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to <i>Helicobacter pylori</i> Lipopolysaccharide

Effect of Purified Lipopolysaccharides from Strains of Helicobacter pylori and Helicobacter felis on Acid Secretion in Mouse Gastric Glands In Vitro

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