title: Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide.
abstract: Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter 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 ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha 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 (CCK2) 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 CCK1 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 CCK2/gastrin receptors.
authors.affiliation: Department of Physiology, Jagiellonian University School of Medicine, Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moran
authors.forename: Robert
authors.initials: R
authors.lastname: Pajdo
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Sliwowski
authors.forename: Danuta
authors.initials: D
authors.lastname: Drozdowicz
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Pawlik
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects*; D000818:Animals; D001241:Aspirin; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D016480:Helicobacter pylori / Q000737:chemistry; D006727:Hormone Antagonists / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood; D020738:Leptin / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D005755:Gastrins; D006727:Hormone Antagonists; D007375:Interleukin-1; D020738:Leptin; D008070:Lipopolysaccharides; D020011:Protective Agents; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D014409:Tumor Necrosis Factor-alpha; C442865:lipopolysaccharide, Helicobacter pylori; C053737:loxiglumide; D011377:Proglumide; D001241:Aspirin; D002211:Capsaicin