Protein kinase C delta-mediated processes in cholecystokinin-8-stimulated pancreatic acini.
OBJECTIVE
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.


METHODS
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.


RESULTS
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(-/-).


CONCLUSIONS
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.
Thrower
Edwin C
EC
Department of Internal Medicine, Veterans Administration Connecticut Healthcare, West Haven, CT 06516, USA. edwin.thrower@yale.edu
Wang
Jeffrey
J
Cheriyan
Salim
S
Lugea
Aurelia
A
Kolodecik
Thomas R
TR
Yuan
Jingzhen
J
Reeve
Joseph R
JR
Gorelick
Fred S
FS
Pandol
Stephen J
SJ
D000098:Acetophenones / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014362:Trypsinogen / Q000378:metabolism
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D016328:NF-kappa B; D010446:Peptide Fragments; C410885:cholecystokinin 8; D014362:Trypsinogen; D002766:Cholecystokinin; C085746:rottlerin; D051745:Protein Kinase C-delta; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000681:Amylases; C070515:bisindolylmaleimide I