STIMULATION OF PANCREATIC AMYLASE RELEASE IS ASSOCIATED WITH A PARALLEL SUSTAINED INCREASE OF CYTOPLASMIC CALCIUM

The kinetics of the changes in the cytoplasmic Ca2+ concentration (Cai2+) and amylase release were measured in fura-2-loaded pancreatic acinar cells and perifused pancreatic acini, respectively. Cholecystokinin octapeptide (CCK-8) and its amphibian analogue caerulein induced similar dose-related increases of Cai2+ and amylase secretion with threshold concentrations of 2-6·10-12 M, and maximal effects at 2·10-10 M. The action of CCK/caerulein on Cai2+ was complex and similar to that of carbachol and bombesin with a prompt several-fold increase within seconds followed by a gradual decline over more than 5 min to a new sustained suprabasal level. The kinetics of amylase release in response to CCK and carbachol correlated with the changes in Cai2+. Additions of the antagonists N2,O2-dibutyrylguanosine 3′:5′-cyclic monophosphate and atropine after 30 min of CCK-8 and carbachol stimulation, respectively, were associated with prompt lowerings of Cai2+ and inhibitions of amylase secretion. The patterns observed with substance P (SP) and eledoisin were different with high concentrations (10-8-10-7 M) giving monophasic increases of Cai2+ and amylase release. An initial stimulation of cells with a high dose of CCK eliminated the Cai2+ response to further stimulation with CCK, carbachol, bombesin and SP, whereas cells subjected to initial stimulation with SP responded to subsequent exposure to CCK with prolonged elevation of Cai2+. The data indicate that stimulation with CCK, carbachol and bombesin may be associated with intracellular mobilization of calcium from more than one pool, and that an increase of Cai2+ is involved even in threshold stimulation of amylase release. © 1990.