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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Tomasz Brzozowski, Peter C. Konturek, Anthony P. Moran, Robert Pajdo, Slawomir Kwiecien, Stanislaw J. Konturek, Zbigniew Sliwowski, Danuta Drozdowicz, Wieslaw W. Pawlik and Eckhart G. Hahn
Journal of Pharmacology and Experimental Therapeutics July 2004, 310 (1) 116-125; DOI: https://doi.org/10.1124/jpet.104.065128
Tomasz Brzozowski
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Peter C. Konturek
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Anthony P. Moran
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Robert Pajdo
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Slawomir Kwiecien
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Stanislaw J. Konturek
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Zbigniew Sliwowski
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Danuta Drozdowicz
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Wieslaw W. Pawlik
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Eckhart G. Hahn
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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-1β, and tumor necrosis factor-α 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.

Footnotes

  • DOI: 10.1124/jpet.104.065128.

  • ABBREVIATIONS:Hp, Helicobacter pylori; LPS, lipopolysaccharide; ASA, aspirin; i.g., intragastric; GBF, gastric blood flow; CCK, cholecystokinin; IL, interleukin; TNF, tumor necrosis factor; RPR-102681, N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido}-3 phenyl}-2 propronique; RIA, radioimmunoassay; RT-PCR, reverse-transcriptase polymerase chain reaction.

    • Received January 8, 2004.
    • Accepted March 15, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 310 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, Issue 1
1 Jul 2004
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Tomasz Brzozowski, Peter C. Konturek, Anthony P. Moran, Robert Pajdo, Slawomir Kwiecien, Stanislaw J. Konturek, Zbigniew Sliwowski, Danuta Drozdowicz, Wieslaw W. Pawlik and Eckhart G. Hahn
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 116-125; DOI: https://doi.org/10.1124/jpet.104.065128

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Tomasz Brzozowski, Peter C. Konturek, Anthony P. Moran, Robert Pajdo, Slawomir Kwiecien, Stanislaw J. Konturek, Zbigniew Sliwowski, Danuta Drozdowicz, Wieslaw W. Pawlik and Eckhart G. Hahn
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 116-125; DOI: https://doi.org/10.1124/jpet.104.065128
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