The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat.
The role played by histamine from enterochromaffin-like (ECL) cells and mast cells in gastric acid secretion and in the development of ethanol-induced gastric lesions was studied in the rat. This was done by examining the effects of inhibition of the histamine-producing enzyme histidine decarboxylase (HDC) with alpha-fluoromethylhistidine (alpha-FMH) and the effects of degranulation of the mucosal mast cells with dexamethasone. A single dose of alpha-FMH (50 mg/kg p.o.) inhibited the HDC activity by 94% but did not affect histamine levels in the gastric mucosa 2 h after dose. Repeated treatment resulted in an almost complete inhibition of HDC activity and in a reduction of histamine levels by 75%. Pentagastrin failed to stimulate acid secretion after 4 days treatment with alpha-FMH, whereas the acid response to histamine was unaffected in chronic gastric fistula rats. Ethanol failed to induce gastric lesions in rats pretreated for 4 days with dexamethasone whereas 4 days pretreatment with alpha-FMH did not influence ethanol-induced lesion formation. The present results show that histamine synthesis is required for pentagastrin-stimulated gastric acid secretion and that mucosal mast-cell histamine plays a role in the development of ethanol-induced gastric lesions.
Andersson
K
K
Department of Biology, AB Hässle, Mölndal, Sweden.
Mattsson
H
H
Larsson
H
H
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D008407:Mast Cells / Q000502:physiology*; D008762:Methylhistidines / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008762:Methylhistidines; D000431:Ethanol; C028309:alpha-fluoromethylhistidine; D003907:Dexamethasone; D006632:Histamine; D006640:Histidine Decarboxylase