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

Abstract

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...

Effect of Probiotics and Triple Eradication Therapy on the Cyclooxygenase (COX)‐2 Expression, Apoptosis, and Functional Gastric Mucosal Impairment in Helicobacter pylori‐Infected Mongolian Gerbils

“…The GBF was determined in H. pylori ‐infected gastric mucosa and compared with that treated with vehicle (saline) using H 2 ‐gas clearance technique as described previously [18]. Immediately after GBF measurement, a venous blood sample was withdrawn from the vena cava into the EDTA containing vials and used for the determination of plasma gastrin levels by radioimmunoassay (RIA) as described elsewhere [19,20].…”

RETRACTION: Role of Angiotensin-(1–7) in Gastroprotection against Stress-Induced Ulcerogenesis. The Involvement of Mas Receptor, Nitric Oxide, Prostaglandins, and Sensory Neuropeptides

“…Thus, the mechanism through which the Ang-(1-7)/Mas receptor axis induced gastroprotection depends on the activation COX/PG system and endogenous PG. Sensory nerves were implicated in the mechanism of gastroprotection against various gastric damaging factors, including stress and Helicobacter pylori lipopolysaccharide (LPS) (Brzozowski et al, 2004;Kwiecien et al, 2007). The gastroprotective and hyperemic activities of Ang-(1-7) were markedly impaired in rats with capsaicin-induced functional ablation of sensory fibers.…”

“…At the termination of 3.5 hours WRS, rats were anesthetized with pentobarbital (60 mg/kg i.p. ), the abdomen was opened, and GBF measured by means of H 2 -gas clearance technique as reported before (Brzozowski et al, 2004(Brzozowski et al, , 2006Kwiecien et al, 2007). The GBF was measured in the fundic part of the gastric mucosa not involving mucosal lesions.…”

Rural Health Alert: Helicobacter pylori in Well Water

“…Peppers with capsaicin can alter the gastric mucosa and therefore may play a role in the pathogenesis of HP. However, some research shows the benefits of capsaicin as a moderator between certain drugs such as aspirin and its erosive effects on the stomach mucosa (Brozowski et al, 2004). Eating hot peppers every day was included as a cofactor for this research.…”