Novel model of integration of signalling pathways in rat pancreatic
acinar cells.
Rivard, Nathalie, Grazyna Rydzewska, Jean-S[acute]ebastien Lods, and
Jean Morisset.
D[acute]epartement de Biologie, Facult[acute]e des Sciences,
Universit[acute]e de Sherbrooke, Sherbrooke, Qu[acute]ebec, Canada,
J1K 2R1
APStracts 2:0071G, 1995.
Cholecystokinin (CCK) is the major pancreatic secretagogue and acinar
cell mitogen. This study was performed to determine by which effector
systems CCK regulates tyrosine kinases (Tyr-k), PTdInositol 3-kinase
and phospholipase D (PLD) activities. Pancreatic acini loaded with 3H
myristic acid or 3H inositol were used to assay PLD and PTdInositol
3-kinase. G protein activation with NaF increased particulate and
crude cytosolic Tyr-ks and PLD activities. PLD activation was
pertussis toxin sensitive. Inhibition of phospholipase C slightly
reduced caerulein-stimulated particulate Tyr-k and blocked crude
cytosolic Tyr-k activity without affecting caerulein-induced PLD
activity. Calcium is an important factor in caerulein stimulation of
Tyr-ks and PLD activities. Protein kinase C and Tyr-ks inhibition
abolished caerulein-activated particulate and crude cytosolic Tyr-k
and PTdInositol 3-kinase activities without any effect on PLD.
Wortmannin inhibited PLD and PTdInositol 3-kinase activation.
Caerulein-induced amylase secretion was partially reduced by Tyr-k
inhibition with no effect from Wortmannin. Caerulein can stimulate a
pertussis toxin-insensitive G protein leading to particulate Tyr-ks
activation and a Ca+2 sensitive cytosolic Tyr-k(s) through PLC
activation. However, PLD activation by caerulein is pertussis toxin
-sensitive, cytosolic calcium sensitive and independent of previous
PLC and Tyr-ks activation.
Received 22 February 1994; accepted in final form 24 March 1995.
APS Manuscript Number G72-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.