AJP - Gastrointestinal and Liver Physiology, Vol 245, Issue 5 676-G680, Copyright © 1983 by American Physiological Society
Effects of inhibitors of cyclic nucleotide phosphodiesterase on actions of cholecystokinin, bombesin, and carbachol on pancreatic acini
J. D. Gardner, V. E. Sutliff, M. D. Walker and R. T. Jensen
In dispersed acini from guinea pig pancreas two inhibitors of cyclic
nucleotide phosphodiesterase, Ro 20-1724 and 3-isobutyl-1-methylxanthine
(IBMX), augmented the increase in amylase secretion caused by supramaximal
concentrations of cholecystokinin but did not alter the stimulation of
enzyme secretion caused by bombesin. The augmentations of the action of
cholecystokinin caused by Ro 20-1724 or IBMX could be reproduced by
8-bromo-cAMP. When tested alone or with theophylline, cholecystokinin did
not alter cAMP in pancreatic acini; however, with Ro 20-1724 or IBMX,
concentrations of cholecystokinin that were supramaximal for stimulating
amylase secretion caused a significant increase in cellular cAMP. These
findings indicate that Ro 20-1724 and IBMX augment the action of
cholecystokinin on enzyme secretion by inhibiting cyclic nucleotide
phosphodiesterase and allowing a significant cholecystokinin-induced
increase in cellular cAMP. IBMX but not Ro 20-1724 caused a parallel
rightward shift in the dose-response curve for the stimulation of amylase
secretion caused by carbachol. IBMX also caused a parallel rightward shift
in the dose-response curve for the stimulation of outflux of 45Ca caused by
carbachol. These results indicate that IBMX, but not Ro 20-1724, can
function as a muscarinic cholinergic antagonist.
