Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2018; 24(8): 882-893
Published online Feb 28, 2018. doi: 10.3748/wjg.v24.i8.882
Relaxin influences ileal muscular activity through a dual signaling pathway in mice
Eglantina Idrizaj, Rachele Garella, Fabio Francini, Roberta Squecco, Maria Caterina Baccari
Eglantina Idrizaj, Rachele Garella, Fabio Francini, Roberta Squecco, Maria Caterina Baccari, Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence 50134, Italy
Author contributions: Idrizaj E and Garella R contributed equally to this work. Idrizaj E and Garella R performed the electrophysiological and the functional experiments, respectively; Baccari MC, Squecco R, Idrizaj E and Garella R designed the research study and analyzed the data; Francini F contributed to design the research study and analyzed the data; Baccari MC and Squecco R wrote the paper; Idrizaj E, Garella R, Francini F, Squecco R and Baccari MC critically revised the manuscript.
Supported by University of Florence (ex 60%) ROBERTASQUECCORICATEN15 (to Squecco R).
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 nr. 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:
Correspondence to: Roberta Squecco, PhD, Research Scientist, Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Viale G.B. Morgagni 63, Florence 50134, Italy.
Telephone: +39-55-2751600 Fax: +39-55-4379506
Received: October 19, 2017
Peer-review started: October 23, 2017
First decision: November 8, 2017
Revised: November 14, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: February 28, 2018

Relaxin (RLX) has been reported to modulate gastrointestinal smooth muscle activity in mice through the L-arginine/NO pathway. However, the possibility that the depressant effects of RLX in ileal preparations could involve additional pathways, not fully elucidated yet, was raised. On these grounds, the present study was designed to investigate the signaling pathways involved in the effects of RLX on ileal preparations. To this aim, we performed experiments using a combined mechanical and electrophysiological approach.

Research frontiers

The actions of RLX occur through a dual signaling pathway that, from a physiological point of view, might represent a reinforcing and cross-talking mechanism for the hormone aimed to guarantee and to prolong its myorelaxant effects in the small intestine.

Innovations and breakthroughs

This study shows, for the first time in ileal preparations, that RLX is able to influence the smooth muscle mechanical and electrophysiological activity through a dual signaling pathway.


The activation of both adenylate cyclase and guanylate cyclase pathways by RLX underlines the physiological importance of the hormone to relax ileal smooth muscle. In this view, it could be speculated that RLX may represent a potential therapeutic tool in those intestinal dysfunctions characterized by hypermotility states.


The modulation of gastrointestinal smooth muscle activity by hormones may be investigated “in vitro” by recording either the mechanical responses or the electrophysiological properties. In ileal preparations, the hormone RLX has been shown to exert a modulatory role by depressing spontaneous contractions and by influencing the electrophysiological activity.