trypsinogen and rottlerin

To define the role of protein kinase C delta (PKC delta) in acinar cell responses to the hormone cholecystokinin-8 (CCK) using isoform-specific inhibitors and a previously unreported genetic deletion model.. Pancreatic acinar cells were isolated from (1) rat, and pretreated with a PKC delta-specific inhibitor or (2) PKC delta-deficient and wild type mice. Isolated cells were stimulated with CCK (0.001-100 nmol/L) and cell responses were measured.. The PKC delta inhibitor did not affect stimulated amylase secretion from rat pancreatic acinar cells. Cholecystokinin-8 stimulation induced a typical biphasic dose-response curve for amylase secretion in acinar cells isolated from both PKC delta(-/-) and wild type mice, with maximal stimulation at 10-pmol/L CCK. Cholecystokinin-8 (100 nmol/L) induced zymogen and nuclear factor kappaB activation in both PKC delta(-/-) and wild type mice, although it was up to 50% less in PKC delta(-/-).. In contrast to previous studies, this study has used specific and complementary approaches to examine PKC delta-mediated acinar cell responses. We could not confirm that it mediates amylase release but corroborated its role in the early stages of acute pancreatitis.

Topics: Acetophenones; Amylases; Animals; Benzopyrans; Calcium-Calmodulin-Dependent Protein Kinases; Cells, Cultured; Cholecystokinin; Dose-Response Relationship, Drug; Enzyme Inhibitors; Immunoblotting; Indoles; Male; Maleimides; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Pancreas; Peptide Fragments; Protein Kinase C-delta; Rats; Rats, Sprague-Dawley; Trypsinogen