AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 3 384-G391, Copyright © 1987 by American Physiological Society
Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors
G. Z. Pan, L. Lu, J. M. Qian and B. G. Xue
In dispersed acini from rat pancreas, it was found that bovine pancreatic
polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at
concentrations of 0.1 and 30 microM, respectively, could significantly
inhibit amylase secretion stimulated by carbachol (P less than 0.01 or
0.05, respectively), and this inhibition by BPP was dose dependent. 45Ca
outflux induced by carbachol was also inhibited by BPP or PP-6, but they
had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated
45Ca outflux. BPP was also capable of displacing the specific binding of
[3H]quinuclidinyl benzilate to its receptors, and it possessed a higher
affinity (ki 35 nM) than carbachol (Ki 1.8 microM) in binding with
M-receptors. It is concluded from this study that BPP acts as an antagonist
of muscarinic cholinergic receptors in rat pancreatic acini. In addition,
BPP inhibited the potentiation of amylase secretion caused by the
combination of carbachol plus secretin or vasoactive intestinal peptide.
This may be a possible explanation of the inhibitory effect of BPP on
secretin-induced pancreatic enzyme secretion shown in vivo, since
pancreatic enzyme secretion stimulated by secretin under experimental
conditions may be the result of potentiation of enzyme release produced by
the peptide in combination with a cholinergic stimulant.
