Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.
Författare
Summary, in English
BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.
Avdelning/ar
- Avdelningen för klinisk kemi och farmakologi
- Drug Target Discovery
Publiceringsår
1996
Språk
Engelska
Sidor
65-959
Publikation/Tidskrift/Serie
Scandinavian Journal of Gastroenterology
Volym
31
Issue
10
Dokumenttyp
Artikel i tidskrift
Förlag
Taylor & Francis
Ämne
- Gastroenterology and Hepatology
Status
Published
Forskningsgrupp
- Drug Target Discovery
ISBN/ISSN/Övrigt
- ISSN: 1502-7708