Effect Of Neuronostatin On Gastrointestinal Motility In Mice

Neuronostatin is a13-amino acid amidated peptide widely distributed in various organs including gastrointestinal tract. Studies have demonstrated that it is a brain/gut peptide with diverse physiological functions. Neuronostatin induces the expression of early response genes c-Fos or c-Jun in neuronal, anterior pituitary, gastrointestinal tissues and cardiomyocytes. Intracerebroventricular administration of neuronostatin in rats leads to a dose-related inhibition of food and water intake, and an increase in mean arterial pressure. It also has abilities to regulate cardiac and cardiomyocyte contractile function, cardiomyocyte survival, neuronal migration. Recently, results from our lab suggest that intracerebroventricular injection of neuronostatin produces antinociceptive effect via the central melanocortin and an opioid system in the tail immersion assay, and induces a depression-like effect via the central melanocortin system in the forced swim test in mice. However, the effect of neuronostatin on gastrointestinal motility has not been well characterized.In the present work, effects of central administration of neuronostatin on gastric emptying, gastrointestinal transit and distal colonic transit were investigated. The results indicated that intracerebroventricular administration of neuronostatin delayed gastric emptying, gastrointestinal transit and distal colonic transit in a dose-related manner in mice. However, it has no influence on distal colonic contractions in vitro. The effects in vivo were significantly reversed by melanocortin3/4receptor antagonist SHU9119or classical opioid receptor antagonist naloxone, suggesting that the central melanocortin system and opioid system may be involved in the gastrointestinal effects elicited by intracerebroventricular administration of neuronostatin. In addition, we found that C-terminal amidation modification of neuronostatin is essential to exert its gastrointestinal effects. These results indicated that neuronostatin may play an important role in regulating gastrointestinal function.