INTRACELLULAR CA2-INDUCED ACUTE-PANCREATITIS IN RATS( RESPONSE OF PANCREATIC ACINI IN CERULEIN)

BACKGROUND/AIMS: To approach the mechanism of impaired signal transduc tion in cerulein-induced pancreatitis, in vitro acinar cell responses including the intracellular Ca2+ dynamics were evaluated. METHODOLOGY: Rats were infused with 10 micro gram /kg/h of cerulein for 4 hours, a nd the pancreas was dispersed. A binding study for I-125-CCK, intracel lular Ca2+ measurement, and an amylase secretion analysis were perform ed in dispersed pancreatic acini. RESULTS: The binding study for I-125 -CCK revealed that the CCK-binding capacity (Bmax) was decreased, alth ough the binding affinities (Kd high and Kd low) were not altered. An in vitro amylase secretion analysis evoked higher basal secretion but little response. In the control acini, the in vitro application of a p hysiological dose of CCK (10 pM) evoked intracellular Ca2+ oscillation s, and a higher dose of CCK (100 pM, 1 nM) evoked a large transient ri se in the intracellular Ca2+ concentration. In cerulein-treated acini, 10 pM CCK evoked no intracellular Ca2+ release, and 100 pM CCK evoked only oscillated Ca2+ concentrations. A higher dose (1 nM) of CCK evok ed a transient rise, but the peak Ca2+ level was significantly lower t han that in the control (p<0.05). CONCLUSIONS: These data suggest that both CCK receptors and intracellular Ca2+ mobilizations are similarly desensitized. The attenuation of amylase secretion is partly due to i mpaired signal transduction, including impaired intracellular Ca2+ rel ease.