Gastric Acid Secretion after Depletion of Enterochromaffin-Like Cell Histamine A Study with α-Fluoromethylhistidine in Rats

Background: Histamine is thought to play a central role in the regulation of gastric acid secretion. In the rat oxyntic mucosa most of the histamine is synthesized and stored in enterochromaffin-like (ECL) cells, and the rest resides in mast cells. The present study examines the role of ECL-cell histamine in the control of acid secretion in the intact, conscious rat. Methods: Rats were treated with α-fluoromethylhistidine (α-FMH) to inhibit histamine synthesis. α-FMH was given by continuous subcutaneous infusion (3 mg/kg/h) for up to 9 days. An additional oral dose of α-FMH (50 mg/kg) was given 2 h before each acid secretion test. Acid secretion was studied in pylorus-ligated rats and in chronic gastric fistula rats stimulated with histamine, gastrin-17, or insulin after 2-6 days of α-FMH infusion. Results: Treatment with α-FMH lowered oxyntic mucosal histamine synthesis by 80%. From previous observations this is thought to reflect depletion of histamine from the ECL cells. The remaining 20% resides in mucosal and submucosal mast cells, which seem to be resistant to α-FMH. Basal acid secretion was inhibited by more than 60% after α-FMH treatment and by more than 80% by ranitidine. Histamine-stimulated secretion was unaffected by α-FMH and abolished by the histamine H2-receptor antagonist ranitidine. The acid response to gastrin-17 was almost abolished in histamine-depleted rats and abolished by ranitidine. Vagally induced acid secretion (provoked by the injection of insulin or by pylorus ligation) was unaffected by α-FMH treatment but abolished by ranitidine and by the muscarinic M1-receptor antagonist pirenzepine. Conclusion: The results suggest that gastrin stimulates acid secretion by releasing histamine from ECL cells. Vagally induced acid secretion is also dependent on a histaminergic pathway but not on ECL-cell histamine.