Effect of loxiglumide on basal and gastrinand bombesin-stimulated gastric acid and serum gastrin levels

Abstract

The effect of the specific cholecystokinin-receptor antagonist loxiglumide on basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg · kg−1 · h−1) significantly augmented basal gastric acid output from 1.8 ± 0.3 to 3.9 ± 0.6 mmol H+/h (P < 0.005) but did not significantly influence integrated basal serum gastrin concentrations (2 ± 21 vs. 32 ± 21 pmol L−1 · h−1). Both gastric acid secretion and integrated serum gastrin concentrations stimulated by bombesin infusion (92.6 pmol · kg−1 · h−1) were significantly augmented by loxiglumide [from 4.0 ± 0.3 to 10.0 ± 1.3 mmol H+/h (P < 0.005) and from 1251 ± 93 to 2558 ± 206 pmol · L−1 · h−1 (P < 0.005), respectively]. Gastric acid output and serum gastrin concentrations during infusion of 5 pmol · kg−1 · h−1 of synthetic human gastrin 17-1 (9.6 ± 2.9 mmol H+/h and 1045 ± 177 pmol · L−1 · h−1) and during infusion of 15 pmol · kg−1 · h−1 of gastrin 17-I (14.5 ± 3.1 mmol H+/h and 2412 ± 312 pmol · L−1 · h−1) were not significantly influenced by loxiglumide (10.3 ± 2.3 mmol H+/h and 1291 ± 257 pmol · L−1 · h−1 for the 5-pmol · kg−1 · h−1 gastrin 17-I infusion dose with loxiglumide and 13.6 ± 3.4 mmol H+/h and 2611 ± 305 pmol · L−1 · h−1 for the 15-pmol · kg−1 · h−1 gastrin 17-I infusion dose with loxiglumide). These data indicate that endogenous cholecystokinin inhibits gastric acid secretion under basal conditions and gastrin release and gastric acid secretion during infusion of bombesin in humans and suggest that the augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may be explained largely by enhanced gastrin release.