AJP - Gastrointestinal and Liver Physiology, Vol 249, Issue 1 100-G107, Copyright © 1985 by American Physiological Society
Effects of proglumide on ductal and basolateral secretion of pancreatic digestive enzymes
C. Niederau, J. H. Grendell and S. S. Rothman
Previous studies have shown that proglumide acts as a cholecystokinin (CCK)
receptor antagonist in isolated pancreatic acini. To establish the effect
of proglumide in the intact organ, its effects on both CCK-stimulated
ductal and basolateral secretion of digestive enzymes were studied in the
in vitro rabbit pancreas. CCK-stimulated ductal secretion of
chymotrypsinogen, amylase, and total protein, as well as basolateral
secretion of amylase, was inhibited by proglumide in a dose-dependent
manner. Regression lines comparing ductal chymotrypsinogen and amylase
outputs also were altered significantly by proglumide in a dose-dependent
manner, with amylase secretion inhibited to a lesser degree. Similarly, the
relative rates of amylase secretion across the ductal versus the
basolateral cell surface were altered, with basolateral secretion inhibited
to a lesser degree. The effects seen with increasing concentrations of
proglumide at a given concentration of CCK mirrored the effects seen with
decreasing the concentration of CCK in the absence of proglumide.
Proglumide did not affect ductal or basolateral secretion stimulated by a
cholinergic agonist and did not affect unstimulated pancreatic secretion.
Thus, proglumide appears to act as a selective antagonist of CCK-stimulated
secretion in the intact organ. The results further indicate that
interactions of an agonist and an antagonist at the CCK receptor can alter
not only the overall amount of enzymes secreted but their relative
proportions as well.
