Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.

Amato, A.; Cinci, Lorenzo; Rotondo, A.; Serio, R; Pellegrini, Maria Simonetta; Vannucchi, Maria; Mulè, F.

Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine- L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinal motility through vagal afferents and central nervous mechanisms; however, no data is available about a direct influence on the gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the spontaneous and evoked mechanical activity of mouse duodenum and colon and to identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle coat. Methods Organ bath recording technique and immunohistochemistry were used. Key Results Glucagon-like peptide-1 (up to the concentration of 1 lmol L)1) failed to affect spontaneous mechanical activity. It caused concentration-dependent reduction of the electrically evoked cholinergic contractions in circular smooth muscle of both intestinal segments, without affecting the longitudinal muscle responses. Glucagon-like peptide-1 inhibitory effect was significantly antagonized by exendin (9–39), an antagonist of GLP-1R. In both intestinal preparations, GLP-1 effect was not affected by guanethidine, a blocker of adrenergic neurotransmission, but it was significantly reduced by Nx-nitro-L-arginine methyl ester, inhibitor of nitric oxide (NO) synthase. Glucagon- like peptide-1 failed to affect the contractions evoked by exogenous carbachol. Immunohistochemistry demonstrated GLP-1R expression in the enteric neurons. Furthermore, 27% of GLP-1R immunoreactive (IR) neurons in the duodenum and 79% of GLP- 1R-IR neurons in the colon, co-expressed nNOS. Conclusions & Inferences The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release.

Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors / Amato A.; Cinci L.; Rotondo A.; Serio R; Faussone-Pellegrini M.S.; Vannucchi M.G.; Mulè F.. - In: NEUROGASTROENTEROLOGY AND MOTILITY. - ISSN 1350-1925. - ELETTRONICO. - 22(2010), pp. 664-672.

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Titolo:	Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.
Autori di Ateneo:	Amato A. CINCI, LORENZO Rotondo A. Serio R PELLEGRINI, MARIA SIMONETTA VANNUCCHI, MARIA Mulè F. mostra contributor esterni nascondi contributor esterni
Autori:	Amato A.; CINCI, LORENZO; Rotondo A.; Serio R; PELLEGRINI, MARIA SIMONETTA; VANNUCCHI, MARIA; Mulè F.
Anno di registrazione:	2010
Rivista:	NEUROGASTROENTEROLOGY AND MOTILITY
Volume:	22
Pagina iniziale:	664
Pagina finale:	672
Abstract:	Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine- L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinal motility through vagal afferents and central nervous mechanisms; however, no data is available about a direct influence on the gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the spontaneous and evoked mechanical activity of mouse duodenum and colon and to identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle coat. Methods Organ bath recording technique and immunohistochemistry were used. Key Results Glucagon-like peptide-1 (up to the concentration of 1 lmol L)1) failed to affect spontaneous mechanical activity. It caused concentration-dependent reduction of the electrically evoked cholinergic contractions in circular smooth muscle of both intestinal segments, without affecting the longitudinal muscle responses. Glucagon-like peptide-1 inhibitory effect was significantly antagonized by exendin (9–39), an antagonist of GLP-1R. In both intestinal preparations, GLP-1 effect was not affected by guanethidine, a blocker of adrenergic neurotransmission, but it was significantly reduced by Nx-nitro-L-arginine methyl ester, inhibitor of nitric oxide (NO) synthase. Glucagon- like peptide-1 failed to affect the contractions evoked by exogenous carbachol. Immunohistochemistry demonstrated GLP-1R expression in the enteric neurons. Furthermore, 27% of GLP-1R immunoreactive (IR) neurons in the duodenum and 79% of GLP- 1R-IR neurons in the colon, co-expressed nNOS. Conclusions & Inferences The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release.
Handle:	http://hdl.handle.net/2158/388254
Appare nelle tipologie:	1a - Articolo su rivista

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