title: Effect of pancreatic polypeptide on gastric accommodation and gastric emptying in conscious rats.
abstract: Pancreatic polypeptide (PP) is an anorexigenic hormone released from pancreatic F cells upon food intake. We aimed to determine the effect of PP on gastric accommodation and gastric emptying in conscious Wistar HAN rats to investigate whether effects on motor function could contribute to its anorexigenic effects. Intragastric pressure (IGP) was measured through a chronically implanted gastric fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml/min). Rats were treated with PP (0, 33 and 100 pmol·kg(-1)·min(-1)) in combination with N(G)-nitro-L-arginine methyl ester (L-NAME; 180 mg·kg(-1)·h(-1)), atropine (3 mg·kg(-1)·h(-1)), or vehicle. Furthermore, the effect of PP was tested after subdiaphragmal vagotomy of the stomach. Gastric emptying of a noncaloric and a caloric meal after treatment with 100 pmol·kg(-1)·min(-1) PP or vehicle was compared using X-rays. PP significantly increased IGP during nutrient infusion compared with vehicle (P < 0.01). L-NAME and atropine significantly increased IGP during nutrient infusion compared with vehicle treatment (P < 0.005 and 0.01, respectively). The effect of PP on IGP during nutrient infusion was abolished in the presence of L-NAME and in the presence of atropine. In vagotomized rats, PP increased IGP compared with intact controls (P < 0.05). PP significantly delayed gastric emptying of both a noncaloric (P < 0.05) and a caloric (P < 0.005) meal. PP inhibits gastric accommodation and delays gastric emptying, probably through inhibition of nitric oxide release. These results indicate that, besides the well-known centrally mediated effects, PP might decrease food intake through peripheral mechanisms.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium; and.
authors.forename: Sofie
authors.initials: S
authors.lastname: Verschueren
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium; and.
authors.forename: Pieter
authors.initials: P
authors.lastname: Janssen
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium; and.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Hultin
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium; and jan.tack@med.kuleuven.ac.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
mesh_terms: D000818:Animals; D003243:Consciousness; D004435:Eating; D002149:Energy Intake; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000008:administration & dosage*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D013997:Time Factors; D014628:Vagotomy
chemical_list: D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D010191:Pancreatic Polypeptide; D019001:Nitric Oxide Synthase
keywords: gastric pressure; nitric oxide; nutrient tolerance; vagus nerve