title: Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms.
abstract: BACKGROUND
  Pancreatic polypeptide (PP) is supposed to be one of the major endogenous agonists of the neuropeptide Y4 receptor. Pancreatic polypeptide can influence gastrointestinal motility, acting mainly through vagal mechanisms, but whether PP acts directly on the stomach has not been explored yet. The aims of this study were to investigate the effects of PP on mouse gastric emptying, on spontaneous tone of whole stomach in vitro and to examine the mechanism of action.
  
  
  METHODS
  Gastric emptying was measured by red phenol method after i.p. PP administration (1-3 nmol per mouse). Responses induced by PP (1-300 mmol L-1) on gastric endoluminal pressure were analyzed in vitro in the presence of different drugs. Gastric genic expression of Y4 receptor was verified by RT-PCR.
  
  
  RESULTS
  Pancreatic polypeptide dose-dependently increased non-nutrient liquid gastric emptying rate. In vitro, PP produced a concentration-dependent contraction that was abolished by tetrodotoxin, a neural blocker of Na+voltage-dependent channels. The contractile response was significantly reduced by atropine, a muscarinic receptor antagonist, and by SR48968, an NK2 receptor antagonist, while it was potentiated by neostigmine, an inhibitor of acetylcholinesterase. The joint application of atropine and SR48968 fully abolished PP contractile effect. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of Y4 receptor mRNA in mouse stomach with a greater expression in antrum than in fundus.
  
  
  CONCLUSIONS
  The present findings demonstrate that exogenous PP stimulates mouse gastric motor activity, by acting directly on the stomach. This effect appears due to the activation of enteric excitatory neurons releasing acetylcholine and tachykinins.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Amato
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Baldassano
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy.
authors.forename: G F
authors.initials: GF
authors.lastname: Caldara
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mulè
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D010191:Pancreatic Polypeptide / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000502:physiology
chemical_list: D018727:Muscarinic Antagonists; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide
keywords: acetylcholine; enteric nervous system; gastric emptying; motility; pancreatic polypeptide; tachykinins