Glucagon-like peptide-2 relaxes mouse stomach through vasoactive intestinal peptide release.
Glucagon-like peptide-2 (GLP-2) influences different aspects of the gastrointestinal function, including epithelial growth, digestion, absorption, motility, and blood flow. Intraluminal pressure from isolated mouse stomach was recorded to investigate whether GLP-2 affects gastric tone and to analyze its mechanism of action. Regional differences between diverse parts of the stomach were also examined using circular muscular strips from fundus and antrum. In the whole stomach, GLP-2 (0.3-100 nM) produced concentration-dependent relaxation with a maximum that was about 75% of relaxation to 1 microM isoproterenol (IC50=2.5 nM). This effect was virtually abolished by desensitization of GLP-2 receptors or by alpha-chymotrypsin. The relaxant response to GLP-2 was not affected by tetrodotoxin, a blocker of neuronal voltage-dependent Na+ channels, but it was significantly reduced by omega-conotoxin GVIA, a blocker of neuronal N-type voltage-operated Ca2+ channels. Nomega-nitro-L-arginine methyl ester, a blocker of nitric oxide synthase, or apamin, a blocker of Ca2+-dependent potassium channels, failed to affect the gastric response to the peptide. However, the relaxation was significantly antagonized by [Lys1,Pro2,5,Arg3,4,Tyr6]VIP7-28, a vasoactive intestinal peptide (VIP) receptor antagonist (GLP-2 maximum effect=45% of relaxation to 1 microM isoproterenol), and virtually abolished by desensitization of the VIP receptors. GLP-2 induced concentration-dependent relaxation in carbachol-precontracted fundic strips but not in antral strips. These results provide the first experimental evidence that GLP-2 is able to induce gastric relaxation acting peripherally on the mouse stomach. The effect appears to be mediated by prejunctional neural release of VIP and confined to fundic region.
Amato
Antonella
A
Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Baldassano
Sara
S
Serio
Rosa
R
Mulè
Flavia
F
D000818:Animals; D002918:Chymotrypsin / Q000494:pharmacology; D017615:Enteric Nervous System / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005748:Gastric Fundus / Q000294:innervation / Q000502:physiology*; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011706:Pyloric Antrum / Q000294:innervation / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D004791:Enzyme Inhibitors; D053767:Glucagon-Like Peptide 2; D026941:Sodium Channel Blockers; D013566:Sympathomimetics; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester