Host-specific differences in the physiology of acid secretion related to prostaglandins may play a role in gastric inflammation and injury.
Immune mediators are involved in strain-specific manifestations of Helicobacter pylori infection, and the type of immune response is associated with production of PGE(2), which in turn influences gastric acid secretion. Acid secretion plays a pivotal role, not only in the pattern of H. pylori-induced gastritis and its consequences, but also in nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathies. Mice and their transgenic modifications are widely used in Helicobacter and eicosanoid research. Using [(14)C]aminopyrine accumulation and pylorus ligation, we aimed to study acid secretion in gastric gland preparations from the commonly used strains of BALB/c and C57BL/6 mice. We found that PGE(2) does not inhibit acid secretion in gastric glands from C57BL/6 mice, in contrast to the expected antisecretory effect of PGE(2) observed in BALB/c mice. In BALB/c mice the effect of histamine and carbachol was reduced by PGE(2), whereas in C57BL/6 mice dose-response curves to these secretagogues were not affected. EP(3) receptors are not involved in acid secretion in C57BL/6 mice, as confirmed by significantly lower expression of mRNA for the EP(3) receptor. These contrary findings are important to the interpretation of the antisecretory role of eicosanoids in BALB/c and C57BL/6 mouse strains and the involvement of prostanoids in the etiology of Helicobacter-induced inflammation and NSAID-induced gastropathies. We propose that the lack of antisecretory effect of PGE(2) observed in C57BL/6 mice could reflect the extent of Helicobacter-induced inflammation and status of acid secretion in response to anti-inflammatory drugs.
Padol
Ireneusz T
IT
Div. of Gastroenterology, McMaster Univ., Health Sciences Centre, Rm. 4W8A, 1200 Main St. West, Hamilton, ON, Canada L8N 3Z5.
Hunt
Richard H
RH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D015232:Dinoprostone / Q000235:genetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology*; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D018078:Receptors, Prostaglandin E / Q000502:physiology; D058308:Receptors, Prostaglandin E, EP3 Subtype
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018679:Cholinergic Agonists; C545648:Ptger3 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D006632:Histamine; D002217:Carbachol; D015232:Dinoprostone