Egf inhibits secretagogue-induced camp production and amylase
secretion by pertussis toxin-sensitive g proteins in pancreatic
acini.
Stryjek-Kaminska, Danuta, Albrecht Piiper, and Stefan Zeuzem.
Medical Department (Dir.: Prof. Dr. W.F. Caspary), University of
Frankfurt/Main, 60590 Frankfurt, Germany
APStracts 2:0108G, 1995.
In pancreatic acinar cells the epidermal growth factor (EGF) receptor
interacts with both cholera toxin- and pertussis toxin-sensitive G
proteins. In the present study isolated rat pancreatic acini were
used to investigate the effect of EGF on basal and secretagogue
-induced cAMP production and amylase release. EGF increased cAMP
production and amylase release in pancreatic acini. However, cAMP
accumulation and amylase release elicited by either vasoactive
intestinal peptide (VIP) or forskolin was inhibited by EGF (17 nM).
EGF inhibited the VIP-induced cAMP production and amylase release
with EC50 of 3 and 2 nM, respectively. EGF had no effect on the
N6,2'-O-dibutyryladenosine 3',5'-monophosphate (dbcAMP)-stimulated
amylase release, suggesting that the inhibitory effect of EGF on the
VIP- and forskolin-induced cAMP production is due to inhibition of
adenylyl cyclase. Pertussis toxin-pretreatment of the acini led to an
increase of the basal, EGF- and VIP-stimulated cAMP accumulation and
amylase release, indicating that pertussis toxin-sensitive G proteins
exert tonic inhibition of adenylyl cyclase even in the absence of
agonist. In pertussis toxin-pretreated acini the inhibitory effect of
EGF on the VIP-induced cAMP production and amylase release was
abolished. In conclusion these results suggest that EGF inhibits
secretagogue-induced cAMP production via activation of pertussis
toxin-sensitive G proteins in rat pancreatic acini, whereas EGF
-induced cAMP production and amylase release occurs via a pertussis
toxin-insensitive pathway.
Received 31 October 1994; accepted in final form 9 May 1995.
APS Manuscript Number G438-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.