Rikkunshito induces gastric relaxation via the β-adrenergic pathway in Suncus murinus

Background: Rikkunshito (RKT) is a gastroprotective herbal medicine. In this study, we investigated the role of RKT in the relaxation of the gastric body (fundus and corpus) and antrum. Methods: We used Suncus murinus, a unique small model animal with similar gastrointestinal motility to humans and dogs. RKT was added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome measure was the intensity of relaxation. The number of spontaneous antral contractions in the absence or the presence of RKT was also counted. Key Results: Rikkunshito induced the relaxation of the gastric body and antrum and decreased the number of spontaneous antral contractions in a dose-dependent manner. The responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N-nitro-l-arginine methyl ester, ritanserin, or ondansetron. On the other hand, timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on the gastric body and antrum and the occurrence of the spontaneous antral contractions. Both butoxamine, a β₂-adrenoreceptor antagonist, and L 748337, a β₃-adrenoreceptor antagonist, but not CGP 20712, a β₁-adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL) gastric relaxation. Conclusions & Inferences: These results indicate that RKT stimulates and modulates gastric relaxation through β₂- and β₃-adrenergic, but not β₁-adrenergic, pathways in S. murinus.