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 mumol 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 N(omega)-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.
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 mumol 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 N(omega)-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.
Authors: Alexander T May; Molly S Crowe; Bryan A Blakeney; Sunila Mahavadi; Hongxia Wang; John R Grider; Karnam S Murthy Journal: Peptides Date: 2018-11-30 Impact factor: 3.750