INTRACELLULAR CA2-VITRO SECRETORY RESPONSE IN ACUTE-PANCREATITIS INDUCED BY A CHOLINE-DEFICIENT, ETHIONINE-SUPPLEMENTED DIET IN MICE( DYNAMICS AND IN)

In order to approach impaired stimulus-secretion coupling in acute pan creatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispe rsed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini, The in vitro amylase secretion analysis of the CDE groups d emonstrated a poor dose-response curve which was significantly lower ( p < 0.01) when 100 pM cholecystokinin (CCK) was administered, Both in CDE and control groups, the application of a physiological dose of CCK -8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amp litude of the oscillations in the CDE groups were not significantly di fferent. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of st imulation both in CDE and control groups. The peak Ca2+ level was lowe r in the CDE groups, but this was not statistically significant. In co nclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis , the pattern of agonist-evoked intracellular Ca2+ release is less aff ected. Other mechanisms subsequent to the onset of intracellular Ca2release are likely to be involved in the inhibition of enzyme secretio n.