Okadaic acid disrupts golgi structure, affects enzyme secretion and
protein synthesis in the stimulated rat exocrine pancreas.
Waschulewski, Ingo H., Marie-Luise Kruse, Brigitte Agricola, Horst F.
Kern, and Wolfgang E. Schmidt.
Laboratory of Molecular Gastroenterology, I. Department of
Medicine, Christian-Albrechts-University of Kiel, D-24105 Kiel; and
Department of Cell Biology and Cell Pathology, Philipps University of
Marburg, D-35037 Marburg, Germany
APStracts 2:0251G, 1995.
Okadaic acid, a serine/threonine phosphatase inhibitor, has been shown
to inhibit rat pancreatic enzyme secretion by interference with late
processes in stimulus-secretion coupling. To further characterize its
action, we studied the effect of okadaic acid on secretion of newly
synthesized proteins, protein synthesis and cellular ultrastructure
in pancreatic lobules derived from rats stimulated in vivo by feeding
the synthetic proteinase inhibitor FOY-305. Okadaic acid completely
blocked protein secretion at concentrations that inhibit the
Ca2+/calmodulin-dependent protein phosphatase 2b calcineurin. Protein
synthesis was abolished at 10-6 mol/l and reduced by 60% at 5.10-7
mol/l okadaic acid. Pancreatic lobules exposed to 5.10-7 mol/l
okadaic acid for 20 min fully restored their secretory capacity upon
removal of the drug, whereas after a preincubation with okadaic acid
for more than 40 min protein secretion remained impaired during the
recovery period. Electron microscopic examination of pancreatic
acinar cells treated with 5.10-7 mol/l okadaic acid revealed a
dilated Golgi complex after 15 and 30 min and a subsequent
fragmentation of Golgi cisternae into clouds of small uniform
vesicles after 60 min. Reassembly of Golgi stacks occurred after a 60
min recovery without ocadaic acid. These data indicate that
serine/threonine phosphatases play an important role not only in the
regulation of pancreatic enzyme synthesis and exocytosis, but are
crucial for the maintenance of normal Golgi architecture and function
in the exocrine rat pancreas. These effects are probably not
exclusively mediated via type 2b calcineurin-like protein
phosphatases.
Received 18 July 1995; accepted in final form 27 November 1995.
APS Manuscript Number G302-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95