Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces a delayed onset hypergastrinemia in rats. The purpose of the present study was to determine if the increased serum gastrin concentrations were caused by decreased gastric acid secretion, decreased plasma clearance of gastrin, and/or decreased gastric emptying. It was found that TCDD treatment decreased gastric acid secretion as determined by decreases in gastric secretory volume, acidity, and total acid output in pylorus-ligated rats. Also, both dose-response and time-course curves for decreased gastric acid secretion in TCDD-treated rats were similar to those for hypergastrinemia. These findings, as well as a significant inverse correlation between serum gastrin concentrations and total gastric acid output in rats treated with graded doses of TCDD (5-100 micrograms/kg), suggest that TCDD-induced decreases in gastric acid production cause elevated serum gastrin concentrations. Neither hypergastrinemia nor decreased gastric acid secretion were observed in pair-fed control rats, demonstrating that neither effect was secondary to undernutrition. The TCDD-induced decrease in gastric acid secretion was not caused by a decrease in the number of acid-secreting parietal cells in the stomach, but rather was associated with a decrease in parietal cell responsiveness to gastrin-elicited acid secretion. This was evidenced by both elevated serum gastrin concentrations and a pharmacological dose of pentagastrin failing to stimulate gastric acid secretion in TCDD-treated rats. The disappearance of iv-administered gastrin-17 from the serum was not affected by TCDD treatment, suggesting that reduced serum gastrin clearance is not responsible for the TCDD-induced hypergastrinemia. Although a marked decrease in gastric emptying of a 51Cr-labeled liquid test meal was also observed in TCDD-treated rats, the lowest dose of TCDD required to produce this effect was greater than that needed to cause hypergastrinemia. This suggests that the hypergastrinemic effect of TCDD is not secondary to a decrease in gastric emptying. We conclude that the most probable cause of hypergastrinemia in TCDD-treated rats is decreased gastric acid secretion.