Pituitary adenylate cyclase activating polypeptide stimulates
cholecystokinin secretion in stc-1 cells.
Chang, Cecilia H., William Y. Chey, Laura Braggins, David H. Coy, and
Ta-Min Chang.
Center for Digestive and Liver Diseases, Department of Medicine,
University of Rochester School of Medicine and Dentistry, Rochester,
New York and Tulane University Medical Center, New Orleans,
Louisiana
APStracts 3:0058G, 1996.
Secretion of cholecystokinin (CCK) from the endocrine cells of small
intestinal mucosa and the murine intestinal tumor cell line, STC-1 is
known to involve both cAMP- and Ca2+-dependent signal transduction
pathways. However, the endogenous stimulant(s) that acts through the
cAMP-dependent cascade has not been identified. We determined the
effect of pituitary adenylate cyclase activating polypeptide (PACAP)
on CCK secretion, cAMP production and its interaction with other CCK
secretagogues in STC-1 cells. At concentrations above 10 nM, PACAP-27
stimulated the release of CCK-LI from STC-1 cells in a time- and
dose-dependent manner. The stimulatory effect of PACAP-27 was
enhanced by the phosphodiesterase inhibitor, 3-isobutyl-1
-methylxanthine (IBMX). PACAP-27, PACAP-38 and vasoactive intestinal
polypeptide (VIP), with or without IBMX, were equally effective and
potent to elicit CCK release with similar half maximal doses and
maximal levels of stimulation. Both forms of PACAP and VIP stimulated
a transient but not significant increase in cellular cAMP level. In
the presence of IBMX, all three peptides increased significantly
cellular cAMP level between 2 to 5 min, but PACAP produced a 2-times
higher level than VIP. The stimulatory effect of PACAP-27 on CCK
release was also potentiated by bombesin and KCl but without a
synergistic production of cAMP. With or without IBMX, PACAP-27
-stimulated CCK secretion was neither affected by a Ca2+ channel
blocker, diltiazem (1 [mu]M), nor a cell permeable Ca2+ chelator,
BAPTA-AM (25 [mu]M), nor by down regulation of protein kinase C. The
stimulatory effects of KCl and bombesin were either reduced or
abolished by these treatments. The synergistic effect of bombesin
with PACAP was abolished by diltiazem and BAPTA-AM but not by down
regulation of protein kinase C; whereas, KCl remained synergistic
with PACAP after these treatments. Taken together these results
indicate that PACAP may be a neuromodulator of CCK secretion that act
through activation of adenylate cyclase, and may function as a co
-regulator with other CCK secretagogues that are known to increase
intracellular Ca2+ concentration.
Received 24 February 1995; accepted in final form 5 February
1996.
APS Manuscript Number G82-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 March 96