Induction by interleukin-1, tumor necrosis factor and lipopolysaccharides of histidine decarboxylase in the stomach and prolonged accumulation of gastric acid.
1. Injection of interleukin-1 (IL-1) into pylorus-ligated rats has been shown strongly to inhibit gastric secretion. However, in the present study, we found that an intraperitoneal injection of IL-1 into intact (non-pylorus-ligated) fasted mice rapidly (within 30 min) induced an accumulation of gastric acid ('early response'). When the dose of IL-1 was larger, the accumulation lasted for a longer period. 2. Injection of IL-1 also caused a later elevation of the activity of histidine decarboxylase (HDC), the histamine-forming enzyme, in the stomach ('later response'). 3. Cimetidine, an antagonist of histamine H2-receptors, suppressed the accumulation of gastric acid in both the early and later periods. An irreversible inhibitor of HDC, alpha-fluoromethylhistidine, partially inhibited the accumulation in the later period. 4. IL-1, when injected 1 h after feeding in mice fasted overnight, markedly retarded gastric emptying. 5. Tumour necrosis factor (TNF) and lipopolysaccharide (LPS) or endotoxin from E. coli both had IL-1-like effects on the stomach, and their effects are presumably mediated by IL-1. 6. These results support the idea that an inhibition of gastric emptying and an elevation of HDC activity in the stomach may explain the findings that a long-lasting accumulation of gastric acid is induced by IL-1 despite its potent inhibition of gastric acid secretion. 7. On the basis of these results, and in the light of the known actions of histamine, the possible roles of IL-1 in gastric inflammation and ulceration are discussed.
Endo
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Department of Pharmacology, School of Dentistry, Tohoku University, Sendai, Japan.
Kumagai
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K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D013270:Stomach / Q000201:enzymology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D006640:Histidine Decarboxylase