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.

Key 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 & Inferences

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.

It is unclear if pancreatic polypeptide (PP) reduces food intake by influencing the gastric motor function and it is not known yet whether PP can act directly on the stomach.

1. The results of the current paper show that PP is able to act peripherally in mouse stomach and to stimulate gastric motility through neural release of acetylcholine and tachykinins acting on NK2 receptors.
2. The PP peripheral action does not appear to represent a satiation signal.

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