Omeprazole: its influence on gastric acid secretion, gastrin and ECL cells.
The H+,K+-ATPase inhibitor omeprazole is a highly effective gastric antisecretory agent, both in animals and man, with a long duration of action. These properties are shared by a number of recently described histamine H2-receptor antagonists. In life-long oncogenicity studies of these H2-receptor antagonists, as well as with the H+,K+-ATPase inhibitor omeprazole, gastric enterochromaffin-like cell (ECL cell) hyperplasia and carcinoids have been found. The purpose of this paper is to summarize available evidence for the "Gastrin Hypothesis" to explain the development of ECL-cell hyperplasia. The hypothesis may be outlined as follows: 1) Inhibition of gastric acid secretion leads to elevated antral pH and, secondarily, to release of gastrin from the antral gastrin cells into the blood stream. 2) Gastrin causes both general hypertrophy of the oxyntic mucosa and hyperplasia of the ECL cells in the oxyntic mucosa. That this sequence of events occurs not only with omeprazole but also with other effective gastric antisecretory agents has been verified in the rat by giving the H2-receptor antagonist ranitidine as a continuous infusion. Ranitidine caused a hypergastrinemia of a similar magnitude as that seen after omeprazole, provided that the acid secretion was inhibited to a similar degree. At similar gastrin levels, ECL-cell hyperplasia of the same magnitude developed during both ranitidine and omeprazole treatment. Antrectomy prevented the development of ECL-cell hyperplasia during omeprazole treatment, indicating that the hyperplasia was not due to the drug treatment per se, but rather to the hypergastrinemia. Both the hypergastrinemia and the ECL-cell hyperplasia were found to be reversible.(ABSTRACT TRUNCATED AT 250 WORDS)
Larsson
H
H
Department of Biology, AB Hässle, Mölndal, Sweden.
Håkanson
R
R
Mattsson
H
H
Ryberg
B
B
Sundler
F
F
Carlsson
E
E
D000818:Animals; D002838:Chromaffin System / Q000187:drug effects*; D004285:Dogs; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000473:pathology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005755:Gastrins / Q000378:metabolism*; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D009853:Omeprazole / Q000009:adverse effects* / Q000494:pharmacology; D011899:Ranitidine / Q000009:adverse effects; D051381:Rats; D013045:Species Specificity
D005755:Gastrins; D011899:Ranitidine; D009853:Omeprazole