Spexin disrupts migrating myoelectric complex in the rat small intestine: The role of galanin-2 and muscarinic receptors

Abstract Spexin (SPX) is an endogenous peptide expressed throughout the gastrointestinal tract. Although its impact on postprandial intestinal motility has been examined, its effect during fasting remains unclear. This study aimed to investigate the direct effects of SPX on jejunal and ileal segments in vitro , its effects on fasting small intestinal motility in vivo , and to determine the roles of galanin-2, muscarinic, and 5-hydroxytryptamine-3 (5-HT₃) receptors in these actions. The contractile responses of rat jejunal and ileal segments to SPX (10⁻⁹–10⁻⁶ M), with or without pretreatment with galanin-2, muscarinic, or 5-HT₃ receptor antagonists (M871, atropine, and ondansetron, respectively) were evaluated in organ baths. For in vivo experiments, bipolar electrodes were implanted at two jejunal sites to record migrating myoelectric complexes (MMC), and a catheter was inserted into the left jugular vein for drug administration. SPX (40–640 µg/kg/h) was infused for 1 hour following basal MMC recording. Antagonists were administered 5 minutes prior to SPX (320 µg/kg/h) infusion. SPX induced concentration-dependent contractions in both intestinal segments, significantly inhibited by M871 but unaffected by atropine or ondansetron. At 160 μg/kg/h, SPX altered the MMC pattern; at 320 μg/kg/h, it disrupted MMC and induced irregular spiking activity, which was blocked by M871 and atropine, but not by ondansetron. These data indicate that SPX modulates fasted motility pattern, involving GALR2-dependent mechanisms and an indirect contribution of muscarinic pathways. These findings may support the development of therapies for gastrointestinal motility disorders. Graphical abstract In vitro , SPX induced concentration-dependent contractions, which were inhibited by M871 but not affected by atropine or ondansetron. In vivo , SPX disrupted the fasting intestinal myoelectric pattern, an effect that was blocked by M871 and atropine but not by ondansetron.