RT Journal Article
SR Electronic
T1 Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa to <em>Helicobacter pylori</em>-Lipopolysaccharide
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 116
OP 125
DO 10.1124/jpet.104.065128
VO 310
IS 1
A1 Tomasz Brzozowski
A1 Peter C. Konturek
A1 Anthony P. Moran
A1 Robert Pajdo
A1 Slawomir Kwiecien
A1 Stanislaw J. Konturek
A1 Zbigniew Sliwowski
A1 Danuta Drozdowicz
A1 Wieslaw W. Pawlik
A1 Eckhart G. Hahn
YR 2004
UL http://jpet.aspetjournals.org/content/310/1/116.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics