Rasagiline, an inhibitor of MAO-B, decreases colonic motility through elevating colonic dopamine content.

BACKGROUND

Dopamine (DA) is a negative modulator of gut motility. Monoamine oxidase-B (MAO-B) is an important metabolic enzyme degrading DA. Rasagiline, an irreversible MAO-B inhibitor, is used to treat Parkinson's disease because of its neuroprotective effect and increasing central DA. However, it is unclear whether MAO-B exists in the colon and rasagiline increases colonic DA, thereby affecting colonic motility.

METHODS

Immunohistochemistry, western blotting, enzyme activity assay, colonic motility recording, gut transit test, and high-performance liquid chromatography-electrochemical detection were employed in this study.

KEY RESULTS

Monoamine oxidase-B was distributed in the colonic muscular layers including neurons and glias of rat and human. When oral treatment of rats with rasagiline for 4 weeks, in vitro colonic motility was significantly reduced, but it was greatly reversed by SCH-23390, an antagonist of DA D receptor. The rasagiline-treated rats also manifested decreased MAO-B activity and increased DA content in the colonic muscular layer, but no alterations were detected in the protein expressions of D and D receptors, and MAO-A and MAO-B, as well as in the content of 5-hydroxytryptamine and noradrenaline. Moreover, acute administration of rasagiline did not affect the colonic motility in vitro and the colonic DA level in rats, although MAO-B activity was significantly inhibited.

CONCLUSIONS & INFERENCES: Monoamine oxidase-B is abundant in the colonic muscular layer including myenteric plexus of rat and human. Long-term administration of rasagiline can increase colonic DA thereby inhibiting colonic motility, suggesting that colonic MAO-B could be a potential drug target for colonic dysmotility.