Psychiatry Investig.  2016 Mar;13(2):232-238. 10.4306/pi.2016.13.2.232.

Olanzapine May Inhibit Colonic Motility Associated with the 5-HT Receptor and Myosin Light Chain Kinase

Affiliations
  • 1Tianjin Mental Health Center, Tianjin, China. daliangsun@yeah.net
  • 2Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3Department of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • 4Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. lizezhi1981@aliyun.com, yangtaiguan@sina.com

Abstract


OBJECTIVE
To study whether the effects of olanzapine on gastrointestinal motility is related to the serotonin antagonism and myosin light chain kinase.
METHODS
Male Sprague-Dawley rats were randomly divided into four groups. Olanzapine gavage was performed for each treatment group during the course of 30 continuous days, while the same volume of saline was given to the rats in the control group. Defecation of the rats was observed on days 7 and 30 after olanzapine gavage. The effects of olanzapine on contraction of colonic smooth muscles were observed in ex vivo experiments. A Western blot was used to evaluate expression levels of the serotonin transporter (SERT) and MLCK in colon segments of the rats.
RESULTS
ResultsaaCompared to the control group, 5-160 µM of olanzapine could inhibit dose-dependently the contraction of colonic smooth muscle ex vivo experiments. The maximum smooth muscle contraction effects of 5-HT and acetylcholine significantly decreased after treatment with 40-160 µM of olanzapine. Constipation was found in the olanzapine-treated rats on day 7 and have sustained day 30 after gavage. Expression of MLCK in olanzapine-treated rats was significantly decreased, whereas the expression of SERT significantly increased on the day 7, then significantly decreased on the day 30 after olanzapine gavage.
CONCLUSION
SERT and MLCK may involve in the inhibition of colonic contraction induced by olanzapine.

Keyword

Antipsychotic agents; Intestinal motility; Serotonin system; Myosin light chain kinase

MeSH Terms

Acetylcholine
Animals
Antipsychotic Agents
Blotting, Western
Colon*
Constipation
Defecation
Gastrointestinal Motility
Humans
Male
Muscle, Smooth
Myosin Light Chains*
Myosin-Light-Chain Kinase*
Myosins*
Rats
Rats, Sprague-Dawley
Serotonin Plasma Membrane Transport Proteins
Serotonin*
Acetylcholine
Antipsychotic Agents
Myosin Light Chains
Myosin-Light-Chain Kinase
Myosins
Serotonin
Serotonin Plasma Membrane Transport Proteins
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