Effects of omeprazole and ranitidine on gastric acid secretion, blood gastrin levels and [3H]-thymidine incorporation in the oxyntic mucosa from dogs and rats.
Dogs provided with a gastric fistula were treated orally for 1 week either with the H+, K+-ATPase inhibitor omeprazole, 80 mumol/kg once daily, or with the histamine H2 receptor antagonist ranitidine, 85-175 mumol/kg every 8 h. Acid secretion, serum gastrin levels and [3H]-thymidine incorporation in the corpus mucosa were determined before, during and after the treatment period. In order to examine differences between species, plasma gastrin levels and [3H]-thymidine incorporation in the oxyntic mucosa were also determined in female rats treated up to 1 week with omeprazole, 400 mumol/kg orally once daily. Histamine-stimulated gastric acid secretion in dogs treated with omeprazole or ranitidine was almost completely inhibited during the whole treatment period. As a consequence of that, the meal-stimulated gastrin levels were increased (7-fold) during treatment by both compounds. [3H]-thymidine incorporation in the dog corpus mucosa was increased approximately 4 times on day 5 both with omeprazole and ranitidine. After the treatment was stopped, gastric acid secretion, serum levels of gastrin and the rate of [3H]-thymidine incorporation were back to control level in both groups within 11 days. In the rats, the plasma gastrin levels increased 10-fold and the rate of [3H]-thymidine incorporation in the corpus mucosa increased 3-fold during treatment with omeprazole. In conclusion, a pronounced suppression of gastric acid secretion over the day with antisecretagogues results in hypergastrinemia in both dogs and rats. As a consequence of the trophic effect of gastrin, the incorporation of [3H]-thymidine in the oxyntic mucosa is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Ryberg
B
B
Department of Biology, AB Hässle, Mölndal, Sweden.
Mattsson
H
H
Carlsson
E
E
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D005755:Gastrins; D011899:Ranitidine; D004247:DNA; D009853:Omeprazole; D013936:Thymidine