Glucagon-like peptide-1 relaxes gastric antrum through nitric oxide in mice.

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Abstract

Glucagon-like-peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the intestinal enteroendocrine-L cells and released after meal ingestion. GLP-1 reduces postprandial glycemia not onlyby its hormonal effects, but also by its inhibitory effects on gastrointestinal motility. Recently, we showed that GLP-1 acts in the enteric nervous system of mouse intestine. Therefore our working hypothesis wasthat GLP-1 may have also a direct influence on the gastric mechanical activity since the major part ofexperimental studies about its involvement in the regulation of gastric motility have been conducted inin vivo conditions. The purposes of this study were (i) to examine exogenous GLP-1 effects on mousegastric mechanical activity using isolated whole stomach; (ii) to clarify the regional activity of GLP-1using circular muscular strips from gastric fundus or antrum; (iii) to analyze the mechanism of actionunderlying the observed effects; (iv) to verify regional differences of GLP-1 receptors (GLP-1R) expressionby RT-PCR. In the whole stomach GLP-1 caused concentration-dependent relaxation significantlyanatagonized by exendin (9–39), an antagonist of GLP-1R and abolished by tetrodotoxin (TTX) or N -nitro-l-arginine methyl ester (l-NAME), inhibitor of nitric oxide (NO) synthase. GLP-1 was without anyeffect in fundic strips, but it induced concentration-dependent relaxation in carbachol-precontractedantral strips. The effect was abolished by TTX or l-NAME. RT-PCR analysis revealed a higher expressionof GLP-1R mRNA in antrum than in fundus. These results suggest that exogenous GLP-1 is able to reducemouse gastric motility by acting peripherally in the antral region, through neural NO release.
Original languageEnglish
Pages (from-to)60-64
Number of pages5
JournalPeptides
Volume32
Publication statusPublished - 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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