Achlorhydria-induced hypergastrinaemia: the role of bacteria.
1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 +/- 11 pmol/l (mean +/- SEM) and 36 +/- 8 pmol/l, respectively, after vehicle, and 153 +/- 30 pmol/l and 181 +/- 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day -1 kg -1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day -1 kg-1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 +/- 11 pmol/l), but further elevated plasma gastrin concentrations to 278 +/- 26 pmol/l in conventional rats (P less than 0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.
J
J
Calam
R A
RA
Goodlad
C Y
CY
Lee
B
B
Ratcliffe
M E
ME
Coates
G W
GW
Stamp
N A
NA
Wright
D000126:Achlorhydria / Q000097:blood*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D005755:Gastrins / Q000097:blood*; D005856:Germ-Free Life / Q000502:physiology*; D016480:Helicobacter pylori / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007958:Leukocyte Count; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology
D005755:Gastrins; D006635:Histamine H2 Antagonists; D014230:Triazoles; C039993:loxtidine