Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.
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.


CONCLUSIONS
ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.
Dept. of Pharmacology, University of Lund, Sweden.
K
K
Andersson
E
E
Lindström
D
D
Chen
H J
HJ
Monstein
A
A
Boketoft
R
R
Håkanson
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D046508:Culture Techniques; D004195:Disease Models, Animal; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000378:metabolism; D005755:Gastrins / Q000097:blood / Q000378:metabolism*; D006632:Histamine / Q000032:analysis / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000187:drug effects / Q000378:metabolism*; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D005755:Gastrins; D008762:Methylhistidines; D012333:RNA, Messenger; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase; D009853:Omeprazole