Gastric acid secretion after depletion of enterochromaffin-like cell histamine. A study with alpha-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 alpha-fluoromethylhistidine (alpha-FMH) to inhibit histamine synthesis. alpha-FMH was given by continuous subcutaneous infusion (3 mg/kg/h) for up to 9 days. An additional oral dose of alpha-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 alpha-FMH infusion.


RESULTS
Treatment with alpha-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 alpha-FMH. Basal acid secretion was inhibited by more than 60% after alpha-FMH treatment and by more than 80% by ranitidine. Histamine-stimulated secretion was unaffected by alpha-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 alpha-FMH treatment but abolished by ranitidine and by the muscarinic M1-receptor antagonist pirenzepine.


CONCLUSIONS
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.
Andersson
K
K
Gastrointestinal Pharmacology and Cell Biology, Astra Hässle AB, Mölndal, Sweden.
Cabero
J L
JL
Mattsson
H
H
Håkanson
R
R
D000818:Animals; D004195:Disease Models, Animal; D004759:Enterochromaffin Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000503:physiopathology; D005755:Gastrins / Q000502:physiology; D006632:Histamine / Q000502:physiology*; D008762:Methylhistidines / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D005755:Gastrins; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine