EFFECT OF DUODENAL JUICE ON BOMBESIN-STIMULATED CHOLECYSTOKININ RELEASE DURING LOXIGLUMIDE ADMINISTRATION IN MAN

Stimulation of cholecystokinin release by bombesin is augmented by cho lecystokinin receptor blockade with loxiglumide. We hypothesize that t his augmented cholecystokinin release results from inhibition of the p ancreatico-biliary response to bombesin during cholecystokinin recepto r blockade. To test this hypothesis, we infused bombesin for 180 min i n six healthy subjects Three bombesin-infusion experiments were perfor med in each subject in random order on different days. In two of these experiments loxiglumide was co-infused with bombesin, while in the th ird experiment saline was co-infused with bombesin. In one of the loxi glumide experiments, duodenal juice, collected on the previous day dur ing infusion of cholecystokinin-GIH, was reperfused intraduodenally du ring the second hour of bombesin infusion. In the saline experiment, t he integrated cholecystokinin response during the first hour of bombes in-infusion (262 +/- 63 pmol 60 min-1) was significantly (P < 0.0 1) h igher than during the second (88 +/- 26 pmol 60 min-1) and third (87 /- 31 pmol 60 min-1) hour of bombesin-infusion. Loxiglumide augmented bombesin-stimulated cholecystokinin secretion from 262 +/- 63 pmol 60 min-1 to 453 +/- 63 pmol 60 min-1 in the first hour of bombesin infusi on (P < 0.01). Integrated cholecystokinin values in the second (489 +/ - 90 pmol 60 min-1) and third (450+/-74 pmol 60 min-1) hour of the lox iglumide experiment, were significantly (P < 0-0 1) higher than in the saline experiment. Duodenal juice significantly (P < 0.05) suppressed cholecystokinin responses from 489 + 90 to 401 + 69 pmol 60 min-1 in the first hour of reperfusion, and from 450 +/- 74 to 300 +/- 85 pmol 60 min-1 in the hour after reperfusion (P < 0.05). However, during and after reperfusion of duodenal juice, cholecystokinin concentrations w ere still distinctly (P < 0.01) higher than in the BBS without loxiglu mide experiment. Since the presence of bombesin-like immunoreactivity in the mucosa of the small intestine permits a role for this neuropept ide in the regulation of cholecystokinin release under physiological c onditions, and since the present study demonstrates that pancreaticobi liary outputs suppress the augmented cholecystokinin response to bombe sin during specific blockade of CCK-receptors, this study supports the concept that pancreatico-biliary components in the duodenum may be in volved in a feedback regulation between pancreaticobiliary products an d cholecystokinin release in man.