A Mondal1, A Takehara1, S Aizawa1, T Tanaka2, N Fujitsuka3, T Hattori3, T Sakai1, I Sakata1. 1. Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan. 2. Faculty of Pharmaceutical Sciences, Josai University, Sakado-shi, Saitama, Japan. 3. Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
Abstract
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 β(2) -adrenoreceptor antagonist, and L 748337, a β(3) -adrenoreceptor antagonist, but not CGP 20712, a β(1) -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 β(2) - and β(3) -adrenergic, but not β(1) -adrenergic, pathways in S. 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 β(2) -adrenoreceptor antagonist, and L 748337, a β(3) -adrenoreceptor antagonist, but not CGP 20712, a β(1) -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 β(2) - and β(3) -adrenergic, but not β(1) -adrenergic, pathways in S. murinus.