In the oxyntic mucosa of the mammalian stomach, histamine is stored in enterochromaffin-like (ECL) cells and in mucosal mast cells. The activity of the histamine-forming enzyme, histidine decarboxylase (HDC), is high in ECL cells but lower in the mucosal mast cells. We studied the consequences of depleting ECL-cell histamine by continuous infusion of the HDC inhibitor a-fluoromethylhistidine (a-FMH) to rat, mouse and hamster, or depleting mucosal mast cell histamine by treating rats with dexamethasone.
In rats at least 80% of oxyntic mucosal histamine was found to reside in ECL cells. Also in mouse and hamster ECL cells appear to be the main storage site for gastric histamine. The ECL cells contain cytoplasmic granules, secretory vesicles and microvesicles. The ultrastructure of the ECL cells was markedly altered by the histamine depletion, but the other endocrine cells in the oxyntic mucosa seemed unaffected. In animals treated with a-FMH the volume occupied by the secretory vesicles was reduced in parallel with a reduction in the mucosal histamine concentration. Gastrin is known to cause histamine release and to have a trophic effect on the oxyntic mucosa. The trophic response has been proposed to be mediated by ECL-cell histamine. Depletion of ECL-cell histamine resulted in an increase in the concentration of HDC mRNA. This was shown to be independent of gastrin since antrectomy did not prevent this increase in a-FMH-treated rats. The increase in HDC mRNA might be mediated via the auto-feedback H3 receptor on the ECL cell. By combining long-term hypergastrinemia with continuous infusion of a-FMH we were able to show that the gastrin-evoked trophic effects in the stomach do not depend on ECL-cell histamine. Histamine has been suggested as one of the candidates behind the development of ethanol-induced gastric lesions. Depletion of mucosal mast cell histamine considerably reduced the development of gastric lesions, whereas depletion of ECL-cell histamine had no effect. Histamine is a key factor in the regulation of gastric acid secretion. Basal acid secretion was reduced and gastrin stimulated acid secretion was abolished in rats treated with a-FMH. Vagally induced acid secretion (by insulin injection or pylorus ligation) was unaffected by a-FMH treatment but inhibited by an H2 antagonist.
The results support the hypothesis that the secretory vesicles represent a major storage site for ECL-cell histamine. We also suggest that gastrin stimulates acid secretion via release of ECL-cell histamine, whereas vagally induced acid secretion does not rely on ECL-cell histamine. A role of mucosal mast cell histamine in the development of ethanol-induced lesions is suggested.
- Division of Clinical Chemistry and Pharmacology
- [unknown], [unknown], Supervisor, External person
|Award date||1996 Feb 22|
|Publication status||Published - 1996|
Place: Dept. of Pharmacology
Name: Panula, Pertti
Affiliation: Åbo, Finland
- Medicinal Chemistry
- Pharmacology and Toxicology
- gastric acid secretion
- a-fluoromethylhistidine (a-FMH)
- oxyntic mucosa
- histidine decarboxylase (HDC)
- Enterochromaffin-like (ECL) cell
- Pharmacological sciences