Site-related Effects of Relaxin in the Gastrointestinal Tract Through Nitric Oxide Signalling: An Updated Report

The peptide hormone relaxin (RLX), in addition to its effects on reproduction, has been reported to influence gastrointestinal motility. Interestingly, the digestive tract has been shown to express RLX receptors and the hormone appears to exert site-specific effects acting at the neural or at the smooth muscle level, mainly by a nitric oxide (NO)-mediated mechanism. NO, released by the enteric nerves and/or smooth muscle cells, is one of the main mediators of gastrointestinal relaxation. In fact, in murine in vitro preparations, RLX depresses organ motility acting at the neural level in the stomach and at the muscular level in the small intestine; conversely, in the colon, this hormone paradoxically increases contractility operating at both neural and muscle levels. These effects are ascribable to the ability of RLX to selectively regulate the expression of the different nitric oxide synthase (NOS) isoforms in the different gastrointestinal tracts. Furthermore, recent electrophysiological experiments have shown that RLX can directly affect the biophysical properties of ileal and colonic smooth muscle cells. This mini-review is intended to offer an update on the site-related actions of RLX on gastrointestinal tract motility in relation with its site-specific effects on NOS isoforms expression. Based on these properties, RLX might be considered a potential therapeutic approach to gastrointestinal motor dysfunctions related to an altered NO production.