Su2058 Chronic Homotypic Stress May Affect GI Functions Through Upregulation of Oxytocin Within PVN-DVC Neurocircuits

Abstract

Background and Aims: Gastric accommodation is a reflex reaction related to gastric reservoir function by which the gastric fundus is relaxed when food enters the stomach. Gastric fundus relaxation induced by accommodation is mediated by nitric oxide (NO), produced by NO neurons. Depletion of NO thus inhibits gastric accommodation. Serotonin (5-HT) 2B receptors exist at the gastric fundus and 5-HT2B receptor activation induces contraction of smoothmuscle. However, the relationship between 5-HT2B receptor and gastric accommodation has not been elucidated. This study investigated the involvement of 5-HT2B receptors and the relationship to NO in gastric accommodation using a conscious guinea pig model. Methods: A polyethylene bag was inserted through the distal part of the gastric body and placed in the proximal stomach of 5-week-old male Hartley guinea pigs. Measurement of gastric accommodation was performed as follows: air (6 mL) was injected into the polyethylene bag at a rate of 2 mL/min, and intrabag pressure at baseline was recorded for 1 min. Immediately after oral administration of a liquid meal (4 mL, 1.7 kcal), air (6 mL) was again injected into the bag, and intrabag pressure was recorded 6 times, for 1 min each time at intervals of 5 min. NG-nitro-L-arginine (L-NNA) (a NO synthase inhibitor; 1-10 mg/kg) or BW723C86 (a 5-HT2B receptor agonist; 5 mg/kg) were administered orally 60 or 20 min before the liquid meal. SB215505 (a 5-HT2B receptor antagonist; 6 mg/kg), rikkunshito (traditional Japanese medicine; 250-1,000 mg/kg), or isoliquiritigenin (component of rikkunshito with 5-HT2B receptor antagonism; 0.125-4 mg/kg) were administered orally 30 min before the liquid meal. Results: Intrabag pressure was significantly decreased 5-25 min after liquid meal administration compared to baseline levels. SB215505 (6 mg/kg) did not affect liquid meal-induced decreases in intrabag pressure. Conversely, BW723C86 (5 mg/kg) significantly inhibited liquid meal-induced decreases in intrabag pressure. The effect of BW723C86 was abolished by co-administration of SB215505 (6 mg/kg). L-NNA dosedependently inhibited liquid meal-induced decreases in intrabag pressure and completely blocked the decrease at a dose of 10 mg/kg (-1.91 ± 0.83 vs. 0.05 ± 1.01 mmHg; p , 0.01). SB215505 (6 mg/kg), rikkunshito (1000 mg/kg), and isoliquiritigenin (4 mg/kg) significantly ameliorated L-NNA (10 mg/kg)-induced inhibition of decreases in intrabag pressure (0.03 ± 1.01 vs. -1.77 ± 0.62 mmHg, p , 0.01; -0.16 ± 0.46 vs. -1.79 ± 0.74 mmHg, p , 0.001; -0.38 ± 0.76 vs. -1.82 ± 0.58 mmHg, p , 0.01). Conclusions: The activation of 5-HT2B receptor inhibits gastric accommodation and may be regulated in part by NO neurons.