The role of Cortistatin-14 in the gastrointestinal motility in mice

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.

Keywords: Cortistatin-14; Gastrointestinal motility; Noradrenaline system; Somatostatin system; c-SOM.