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Rasagiline, an inhibitor of MAO ‐B, decreases colonic motility through elevating colonic dopamine content
Author(s) -
Liu C.Z.,
Zhang X.L.,
Zhou L.,
Wang T.,
Quan Z.S.,
Zhang Y.,
Li J.,
Li G.W.,
Zheng L.F.,
Li L.S.,
Zhu J.X.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13390
Subject(s) - rasagiline , motility , monoamine oxidase b , monoamine oxidase , chemistry , dopamine , endocrinology , medicine , monoamine neurotransmitter , pharmacology , receptor , enzyme , serotonin , biology , parkinson's disease , biochemistry , microbiology and biotechnology , disease
Abstract 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 1 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 1 and D 2 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.