JinHong Jiang1, WeiDong Jin1, YaLi Peng1, XueYa Liang1, Shu Li1, LiJuan Wei1, ZhiPing Lei1, LongFei Li1, Min Chang2. 1. Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, China. 2. Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, China. Electronic address: changmin@lzu.edu.cn.
Abstract
BACKGROUND: This study aimed to investigate the functional roles of Cortistatin-14 (CST-14) in the gastrointestinal (GI) motility. METHODS: For in vivo study, mice were randomly divided into control, ip injected CST-14 (0.1, 0.5, 1, 5, 10mg/kg)+control group, icv injected CST-14 (5μg)+control group, dextran sulfate sodium-induced colitis group, CST-14+colitis group, castor oil-induced diarrhea group, CST-14+diarrhea group. We carried out these experiments by quantitative real-time PCR, GI transit, bead expulsion and fecal pellet output. For in vitro study, effects of CST-14 were investigated in the longitudinal and circular muscle contractions of jejum, ileum, and colon. RESULTS: In vivo, the expression of CST-14 mRNA was significantly decreased in the colon of colitis mice and CST-14 significantly inhibited GI transit rate in colitis mice, and delayed the emergence of liquid feces in castor oil-induced diarrhea mouse model. Additionally, ip injection of CST-14, but not icv injected, remarkably inhibited GI transit, bead expulsion and fecal pellet output in mice. In vitro assays, CST-14 (10-6M) could relax the rhythms of the longitudinal muscles and circular muscles of the jejunum, ileum and colon of mice. The further study indicated that the roles of CST-14 in mouse GI motility were significantly reversed by c-SOM (sstr1-5 antagonist), especially sstr2 and sstr3 and propranolol (β-adrenoceptor blocker), suggesting that somatostatin system and noradrenaline system were involved in the inhibiting effects of CST-14 in GI. CONCLUSION: Such inhibiting effects imply that CST-14 system in gastrointestinal motility might be a new target for treatment of GI tract disorder.
BACKGROUND: This study aimed to investigate the functional roles of Cortistatin-14 (CST-14) in the gastrointestinal (GI) motility. METHODS: For in vivo study, mice were randomly divided into control, ip injected CST-14 (0.1, 0.5, 1, 5, 10mg/kg)+control group, icv injected CST-14 (5μg)+control group, dextran sulfate sodium-induced colitis group, CST-14+colitis group, castor oil-induced diarrhea group, CST-14+diarrhea group. We carried out these experiments by quantitative real-time PCR, GI transit, bead expulsion and fecal pellet output. For in vitro study, effects of CST-14 were investigated in the longitudinal and circular muscle contractions of jejum, ileum, and colon. RESULTS: In vivo, the expression of CST-14 mRNA was significantly decreased in the colon of colitismice and CST-14 significantly inhibited GI transit rate in colitismice, and delayed the emergence of liquid feces in castor oil-induced diarrheamouse model. Additionally, ip injection of CST-14, but not icv injected, remarkably inhibited GI transit, bead expulsion and fecal pellet output in mice. In vitro assays, CST-14 (10-6M) could relax the rhythms of the longitudinal muscles and circular muscles of the jejunum, ileum and colon of mice. The further study indicated that the roles of CST-14 in mouse GI motility were significantly reversed by c-SOM (sstr1-5 antagonist), especially sstr2 and sstr3 and propranolol (β-adrenoceptor blocker), suggesting that somatostatin system and noradrenaline system were involved in the inhibiting effects of CST-14 in GI. CONCLUSION: Such inhibiting effects imply that CST-14 system in gastrointestinal motility might be a new target for treatment of GI tract disorder.