Effect of the specific cholecystokinin-receptor antagonist loxiglumide on bombesin stimulated pancreatic enzyme secretion in man

Abstract

We have investigated the effects of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on basal and bombesin stimulated pancreatic enzyme secretion, bilirubin output and plasma CCK release in six healthy subjects. The data were compared with those obtained in control experiments where saline was infused instead of loxiglumide. Basal amylase output (4.7 ± 0.8 kU/45 min), trypsin output (2.9 ± 0.8 kU/45 min) and bilirubin output (7.7 ± 2.8 mmol/45 min) gradually declined during infusion of loxiglumide to values of 1.3 ± 0.3 kU/45 min, 0.5 ± 0.1 kU/45 min and 0.4 ± 0.0 mmol/45 min, respectively, reaching statistical significance ( P < 0.05) in the 30 to 45-min period after the start of the loxiglumide infusion. In the control experiments saline infusion failed to influence basal amylase, trypsine and bilirubin output, while bombesin stimulated amylase output from 4.7 ± 0.8 kU/45 min to 25.1 ± 5.1 kU/45 min ( P < 0.05), trypsin output from 2.9 ± 0.8 kU/45 min to 11.6 ± 2.0 kU/45 min ( P < 0.05) and bilirubin output from 7.7 ± 2.8 mmol/45 min to 68.0 ± 16.0 mmol/45 min ( P < 0.05). Loxiglumide failed to significantly influence bombesin stimulated amylase output (36.7 ± 9.0 kU/45 min) and trypsin output (8.3 ± 2.9 kU/45 min), but almost abolished bilirubin output (9.7 ± 3.6 mmol/45 min) ( P < 0.05). Basal plasma CCK (2.4 ± 0.1 pM) was not significantly influenced by loxiglumide (2.4 ± 0.2 pM). Against a background infusion of saline bombesin significantly stimulated plasma CCK levels at all time points ( P < 0.01) with a gradual decline after the first 15-min sample. Loxiglumide significantly ( P < 0.05) augmented bombesin stimulated plasma CCK at all time intervals without such a decline. These data demonstrate that: (1) basal pancreatic enzyme secretion and gallbladder motility are inhibited by loxiglumide, (2) bombesin-stimulated gallbladder contraction, but not pancreatic enzyme secretion is inhibited by loxiglumide, (3) bombesin-stimulated CCK release is augmented by loxiglumide, which could not be explained by inhibition of pancreatic enzyme secretion.