Pancreatic polypeptide inhibits pancreatic enzyme secretion via a cholinergic pathway.
In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP [PP-(31-36)] inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with [3H] choline, PP(31-36) inhibited the potassium-evoked release of synthesized [3H] acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function.
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010191:Pancreatic Polypeptide / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D010446:Peptide Fragments; C036964:pancreatic polypeptide (31-36); D018738:Hexamethonium; D010191:Pancreatic Polypeptide; D014701:Veratridine; D001285:Atropine; D000681:Amylases; D012844:Sincalide; D002794:Choline; D000109:Acetylcholine; D011188:Potassium