Gastric acid secretion after depletion of enterochromaffin-like cell histamine. A study with a-fluoromethylhistidine in rats
Författare
Summary, in English
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. 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.
Avdelning/ar
- Drug Target Discovery
Publiceringsår
1996
Språk
Engelska
Sidor
24-30
Publikation/Tidskrift/Serie
Scandinavian Journal of Gastroenterology
Volym
31
Issue
1
Dokumenttyp
Artikel i tidskrift
Förlag
Taylor & Francis
Ämne
- Basic Medicine
Status
Published
Forskningsgrupp
- Drug Target Discovery
ISBN/ISSN/Övrigt
- ISSN: 1502-7708