Oxytocin Inhibits Fasted Jejunal Motility in Rats via OTRs and Partial GLP-1R Involvement

The migrating myoelectric complex (MMC) is a crucial pattern of electrical activity that drives fasting small intestinal motility, clearing undigested material. Dysregulation of MMC can contribute to various gastrointestinal motility disorders. While oxytocin (OT) is known to influence diverse physiological functions, including some gastrointestinal processes through oxytocin receptors (OTRs), its specific role in regulating jejunal MMC activity during fasting has remained largely unexplored. Understanding this mechanism could open new avenues for therapeutic interventions in conditions characterized by altered gut motility, potentially involving interactions with other key pathways like glucagon-like peptide-1 receptors (GLP-1Rs) or nitric oxide (NO) signaling.

This study utilized adult male Sprague Dawley rats, surgically implanted with bipolar electrodes at three jejunal sites to record MMC activity. After a recovery period and 18 hours of fasting, baseline recordings were taken for one hour. Subsequently, Oxytocin was administered intraperitoneally (IP) at doses of 4-32 µg/kg. To elucidate the underlying mechanisms, rats were pretreated with specific antagonists: the OTR antagonist atosiban 2 mg/kg, the GLP-1R antagonist exendin (9-39) 200 µg/kg, or the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA) 5 mg/kg, before receiving Oxytocin 16 µg/kg. The primary endpoints were changes in jejunal spike frequency and MMC cycle number compared to vehicle control.

Oxytocin administration significantly reduced both jejunal spike frequency and MMC cycle number in a dose-dependent manner, with effects observed across the 4-32 µg/kg range (p < 0.05-0.001 vs. vehicle). This inhibitory action was largely mediated by OTRs. Specifically, pretreatment with the OTR antagonist atosiban 2 mg/kg completely reversed the oxytocin-induced reduction in spike frequency and MMC cycle number (p < 0.001 vs. oxytocin alone), indicating a direct OTR-dependent mechanism. Furthermore, the GLP-1R antagonist exendin (9-39) 200 µg/kg partially attenuated these inhibitory effects (p < 0.01-0.001 vs. oxytocin alone), suggesting a partial involvement of GLP-1R signaling in oxytocin's action on jejunal motility.

The nitric oxide synthase inhibitor L-NNA 5 mg/kg had no significant effect on oxytocin's actions, ruling out the involvement of NO pathways in this context.