Original ArticlesProtein Kinase C δ-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic AciniThrower, Edwin C. PhD*†; Wang, Jeffrey MD‡§; Cheriyan, Salim BS*†; Lugea, Aurelia PhD‡§; Kolodecik, Thomas R. MS*†; Yuan, Jingzhen PhD‡§; Reeve, Joseph R. Jr PhD‡§; Gorelick, Fred S. MD*†; Pandol, Stephen J. MD‡§ Author Information From the *Department of Internal Medicine, Section of Digestive Diseases, Veterans Administration Connecticut Healthcare, West Haven; †Yale University School of Medicine, New Haven, CT; ‡Research Center for Alcoholic Liver and Pancreatic Diseases, Veterans Affairs Greater Los Angeles Health Care System; and §University of California, Los Angeles, CA. Received for publication January 14, 2009; accepted July 16, 2009. Reprints: Edwin C. Thrower, PhD, Veterans Administration Medical Center, 950 Campbell Ave, Bldg 4, West Haven, CT 06516 (e-mail: [email protected]). This work was supported by a National Institutes of Health grant R21 (DK69702 to E.C.T.), National Institutes of Health Grants RO1 (DK33850 to J.R.R., Jr; DK54021 to F.S.G.), USC-UCLA Research Center for Alcoholic Liver and Pancreatic Injury grant (5 P60 AA11999 from NIAAA; Tsukamoto; to S.J.P.), and a Veterans Administration Merit and Senior Career Development Award (to F.S.G.). Pancreas: November 2009 - Volume 38 - Issue 8 - p 930-935 doi: 10.1097/MPA.0b013e3181b8476a Buy Metrics Abstract Objectives: To define the role of protein kinase C δ (PKC δ) in acinar cell responses to the hormone cholecystokinin-8 (CCK) using isoform-specific inhibitors and a previously unreported genetic deletion model. Methods: Pancreatic acinar cells were isolated from (1) rat, and pretreated with a PKC δ-specific inhibitor or (2) PKC δ-deficient and wild type mice. Isolated cells were stimulated with CCK (0.001-100 nmol/L) and cell responses were measured. Results: The PKC δ 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 δ−/− and wild type mice, with maximal stimulation at 10-pmol/L CCK. Cholecystokinin-8 (100 nmol/L) induced zymogen and nuclear factor κB activation in both PKC δ−/− and wild type mice, although it was up to 50% less in PKC δ−/−. Conclusions: In contrast to previous studies, this study has used specific and complementary approaches to examine PKC δ-mediated acinar cell responses. We could not confirm that it mediates amylase release but corroborated its role in the early stages of acute pancreatitis. © 2009 Lippincott Williams & Wilkins, Inc.