Actions of natural gastric inhibitory peptide on pancreatic acinar cells: Due to contamination with cholecystokinin

Abstract

In dispersed acini from guinea pig pancreas, purified natural porcine gastric inhibitory peptide stimulated amylase secretion and potentiated the increase in amylase secretion caused by secretin, vasoactive intestinal peptide, and 8-bromo-cyclic adenosine 5′-monophosphate, but did not alter the increase in enzyme secretion caused by bombesin, carbachol, or cholecystokinin. Gastric inhibitory peptide also increased outflux of 45Ca from pancreatic acini but did not alter cellular cyclic adenosine 5′-monophosphate. These effects appeared to result from the ability of the peptide to occupy cholecystokinin receptors on pancreatic acini because the peptide's effects on acinar cell function correlated closely with its ability to inhibit binding of 125I-cholecystokinin to pancreatic acini and because dibutyryl cyclic guanosine 5′-monophosphate, a specific cholecystokinin-receptor antagonist, abolished the stimulation of enzyme secretion caused by gastric inhibitory peptide. Moreover, the relative potencies with which gastric inhibitory peptide and cholecystokinin inhibited binding of 125I-cholecystokinin to acinar cell receptors were the same as their relative potencies for inhibiting binding of 125I-cholecystokinin to cholecystokinin-specific antiserum. Finally, chromatography of the preparation of natural gastric inhibitory peptide revealed two protein peaks, neither of which contained cholecystokininlike immunoreactivity or altered pancreatic acinar cell function, plus a third peak that eluted in the same position as native cholecystokinin, contained cholecystokininlike immunoreactivity, and stimulated amylase secretion from pancreatic acini. These results indicate that natural porcine gastric inhibitory peptide is contaminated by cholecystokinin and that it is this contaminating cholecystokinin that accounts for the ability of natural gastric inhibitory peptide to alter acinar cell function.