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.