title: Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors.
abstract: 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.
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010189:Pancreatic Juice / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012633:Secretin / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011976:Receptors, Muscarinic; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D010191:Pancreatic Polypeptide; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol; D000242:Cyclic AMP; D000681:Amylases; D012844:Sincalide; D002118:Calcium