Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7211-7220
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7211
Glucagon-like peptide-2 modulates the nitrergic neurotransmission in strips from the mouse gastric fundus
Rachele Garella, Eglantina Idrizaj, Chiara Traini, Roberta Squecco, Maria Giuliana Vannucchi, Maria Caterina Baccari
Rachele Garella, Eglantina Idrizaj, Roberta Squecco, Maria Caterina Baccari, Department of Experimental and Clinical Medicine, Section of Physiology, University of Florence, 50134 Florence, Italy
Chiara Traini, Maria Giuliana Vannucchi, Department of Experimental and Clinical Medicine, Histology and Embryology Research Unit, University of Florence, 50134 Florence, Italy
Author contributions: Garella R and Idrizaj E contributed equally to this work; Garella R, Idrizaj E and Squecco R performed the functional experiments; Traini C performed the immunohistochemical experiments and the image analysis; Baccari MC, Garella R and Idrizaj E designed the research study and analyzed the data; Vannucchi MG contributed to design the research study and analyzed the data; Baccari MC wrote the paper; Garella R, Idrizaj E, Traini C, Vannucchi MG and Baccari MC critically revised the manuscript.
Supported by University of Florence (ex 60%) RICATEN14-16 to Baccari MC.
Institutional animal care and use committee statement: The experimental protocol was designed in compliance with the guidelines of the European Communities Council Directive 2010/63/UE and the recommendations for the care and use of laboratory animals approved by the Animal Care Committee of the University of Florence, Italy, with authorization from the Italian Ministry of Health No. 787/2016-PR.
Conflict-of-interest statement: No conflicts of interest, financial or otherwise, are declared by the authors.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maria Caterina Baccari, PhD, Associate Professor, Department of Experimental and Clinical Medicine, Section of Physiology, University of Florence, Viale G.B. Morgagni 63, 50134 Florence, Italy. mcaterina.baccari@unifi.it
Telephone: +39-55-2751600 Fax: +39-55-4379506
Received: June 8, 2017
Peer-review started: June 8, 2017
First decision: August 10, 2017
Revised: August 4, 2017
Accepted: September 26, 2017
Article in press: September 26, 2017
Published online: October 28, 2017
Processing time: 143 Days and 16.5 Hours
Abstract
AIM

To investigate whether glucagon-like peptide-2 (GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available.

METHODS

For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation (EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of GLP-2 (2 and 20 nmol/L) were evaluated on the neurally-induced contractile and relaxant responses elicited by EFS. Neuronal nitric oxide synthase (nNOS) enzyme was evaluated by immunohistochemistry.

RESULTS

In the functional experiments, electrical field stimulation (EFS, 4-16 Hz) induced tetrodotoxin (TTX)-sensitive contractile responses, which were reduced in amplitude by GLP-2 (P < 0.05). In the presence of the nitric oxide (NO) synthesis inhibitor L-NNA, GLP-2 no longer influenced the neurally-evoked contractile responses (P > 0.05). The direct smooth muscle response to methacholine was not influenced by GLP-2 (P > 0.05). In the presence of guanethidine and carbachol, the addition of GLP-2 to the bath medium evoked TTX-sensitive relaxant responses that were unaffected by L-NNA (P > 0.05). EFS induced a fast NO-mediated relaxation, whose amplitude was enhanced in the presence of the hormone (P < 0.05). Immunohistochemical experiments showed a significant increase (P < 0.05) in nNOS immunoreactivity in the nerve structures after GLP-2 exposure.

CONCLUSION

The results demonstrate that in gastric fundal strips, GLP-2 influences the amplitude of neurally-induced responses through the modulation of the nitrergic neurotransmission and increases nNOS expression.

Keywords: Immunohistochemistry; Gastric motility; Glucagon-like peptide-2; Neuronal nitric oxide synthase; Non-adrenergic non-cholinergic neurotransmission

Core tip:The results of the present study demonstrate for the first time that, in strips from the mouse gastric fundus, glucagon-like peptide-2 (GLP-2) depresses the amplitude of the neurally-induced contractile responses and enhances the amplitude of the relaxant ones through the modulation of the nitrergic neurotransmission. GLP-2 also increases neuronal nitric oxide synthase immunoreactivity in the nerve structures. All these inhibitory effects might contribute to gastric relaxation, thus increasing the organ capacity. Since gastric distension represents a peripheral satiety signal from a physiological point of view, it could be speculated that the relaxant effects of GLP-2 might concur to suppress feeding behavior in rodents.