Acid blockade by omeprazole or ICI 162846 in a chronic duodenal ulcer model.
Oral treatment with the H2-antagonist ICI 162,846 or omeprazole for five days inhibited both basal and pentagastrin stimulated acid secretion by 50% or more in mice. Either treatment increased the luminal secretion of histamine in the basal (12-fold) and stimulated (9-fold) states. Mice treated with the H2-antagonist had a 27% reduction (p less than 0.05) in mural histamine in the acid-producing area of the stomach. Mice were treated so as to induce duodenal ulcers (abscopal model) and were then treated with the H2-antagonist ICI 162,846, omeprazole or vehicle, orally for one week. Fewer duodenal ulcers were found in animals receiving drug treatments than in the oral vehicle group. Both the H2-receptor antagonist and the proton pump blocker inhibit acid production; acid blockade by either drug is accompanied by a massive increase in secretion of histamine. This rise was associated with depletion of the gastric histamine store only with H2-receptor blocker. Both means of acid inhibition reduce the formation of ulcers in this model.
Gompertz
R H
RH
Department of Surgery, Royal Postgraduate Medical School, London, UK.
Man
W K
WK
Li
S K
SK
Spencer
J
J
Baron
J H
JH
Michalowski
A S
AS
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D004381:Duodenal Ulcer / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D006632:Histamine / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D008482:Mediastinum / Q000528:radiation effects; D051379:Mice; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D006635:Histamine H2 Antagonists; D011720:Pyrazoles; D006632:Histamine; C049056:ICI 162846; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole