Gastrin receptor antagonist YM022 prevents hypersecretion after long-term acid suppression

Female rats were treated orally for 13 wk with YM022 (300 mumol.kg-1.day-1) and with omeprazole (400 mumol.kg-1.day-1) or famotidine (900 mumol.kg-1.day-1) with or without YM022. At 2 h after the last dose, YM022 and omeprazole markedly inhibited basal and pentagastrin-induced acid secretion. Famotidine was less potent than YM022 and omeprazole against both secretions. The degree of increase in plasma gastrin level in the three groups was parallel to the antisecretory potencies of the drugs. At 14 days after the cessation of omeprazole treatment, the secretory response to pentagastrin increased above that of the control. This hyperresponse lasted for > or = 56 days. In the famotidine-treated group, a small increase in secretory response to pentagastrin was observed but was not statistically significant. The increase in secretory response to pentagastrin was paralleled by an increase in mucosal cell mass. In contrast, YM022 not only exhibited a long-lasting inhibition of pentagastrin-induced acid secretion but also prevented the hyperresponse to pentagastrin caused by omeprazole. These results indicate that the hypergastrinemia caused by long-term administration of antisecretory drugs increases mucosal secretory response to pentagastrin through a gastrin/cholecystokinin B receptor-mediated pathway in rats.

Eel calcitonin suppresses plasma human calcitonin levels in medullary carcinoma of the thyroid

1. The effects of synthetic [Asu1,7]-eel calcitonin (0.5 MRC unit/kg body weight intravenously for 30 min) on circulating levels of human calcitonin, calcium and gastrin were investigated in five patients with medullary carcinoma of the thyroid. 2. Blood samples were obtained before and 15, 30, 60, 90, 120 and 180 min after commencement of infusion of [Asu1,7]-eel calcitonin. Plasma levels of human calcitonin were measured by radioimmunoassay. Cross-reactivity with [Asu1,7]-eel calcitonin in this assay was negligible. 3. On infusion of [Asu1,7]-eel calcitonin, the mean plasma level of human calcitonin decreased significantly to 71.0 ± 8.7% of the basal level (mean ± sem, P < 0.05) after 30 min and 68.4 ± 25.4% of the basal level (P < 0.05) after 60 min. The serum calcium level also decreased significantly, but lagged behind the decrease of human calcitonin, being 95.1 ± 0.7% of the basal level (P < 0.01) at 120 min and 94.8 ± 0.6% of the basal level (P < 0.02) at 180 min. The mean plasma gastrin level did not change significantly on infusion of [Asu1,7]-eel calcitonin. 4. In pooled data for all times, the percentage change in human calcitonin was not significantly correlated with either the percentage change in calcium (r = −0.25, P > 0.1) or the percentage change in gastrin (r = −0.3 8, P > 0.1). 5. These data suggested that [Asu1,7]-eel calcitonin suppressed calcitonin secretion in patients with medullary carcinoma of the thyroid. The mechanism of its effect is unknown.

Plasma secretin and gastrin responses to a meat meal and duodenal acidification in dogs

In five conscious dogs with gastric fistula and two duodenal cannulas, plasma RIA secretin and gastrin levels were determined in response to 1) infusion of 0.1 N HCl in the proximal duodenal cannula, 2) ingestion of a meal, and 3) intraduodenal infusion of 0.1 N HCl following ingestion of a meal. Significant increases in plasma RIA secretin levels occurred during duodenal acidification. However, no significant change occurred in the secretin levels after ingestion of a meal, whereas significant increase in plasma gastrin level was observed. Postprandial duodenal pH remained above 4.5 for 3 h.