Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine-induced Parkinson's disease rats.

Abstract

Constipation is common in Parkinson's disease (PD), in which monoamines (dopamine [DA], norepinephrine [NE], and 5-hydroxytryptamine [5-HT]) play an important role. Rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra (SN) exhibit constipation, but the role of monoamines and their receptors is not clear. In the present study, colonic motility, monoamine content, and the expression of monoamine receptors were examined using strain gauge force transducers, ultraperformance liquid chromatography tandem mass spectrometry, immunofluorescence, and Western blot. The 6-OHDA rats displayed a significant reduction in dopaminergic neurons in the SN and a decreased time on rota-rod test and a marked decrease in daily fecal production and fecal water content. The amplitude of colonic spontaneous contraction was obviously decreased in 6-OHDA rats. Blocking D1-like receptor and β3-adrenoceptor (β3-AR) significantly reduced the inhibition of DA and NE on the colonic motility, respectively, whereas the 5-HT and 5-HT4 receptor agonists promoted the colonic motility. Moreover, DA content was increased in the colonic muscularis externa of 6-OHDA rats. The protein expression of β3-ARs was notably upregulated, but 5-HT4 receptors were significantly decreased in the colonic muscularis externa of 6-OHDA rats. We conclude that enhanced DA and β3-ARs and decreased 5-HT4 receptors may be contributed to the colonic dysmotility and constipation observed in 6-OHDA rats.

• Authors: Xiaoli Zhang, Yun Li, Chenzhe Liu, Ruifang Fan, Ping Wang, Lifei Zheng, Feng Hong, Xiaoyan Feng, Yue Zhang, Lisheng Li, Jinxia Zhu
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 166 Issue 2 Pg. 152-62 (Aug 2015) ISSN: 1878-1810 [Electronic] United States
• PMID: 25766133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Biogenic Monoamines
• Receptors, Adrenergic, beta-3
• Receptors, Biogenic Amine
• Receptors, Dopamine
• Receptors, Serotonin
• Serotonin
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Norepinephrine

Topics

• Animals
• Biogenic Monoamines (metabolism)
• Colon (metabolism, pathology, physiopathology)
• Gastrointestinal Motility
• Male
• Norepinephrine (metabolism)
• Oxidopamine
• Parkinson Disease (metabolism, pathology, physiopathology)
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta-3 (metabolism)
• Receptors, Biogenic Amine (metabolism)
• Receptors, Dopamine (metabolism)
• Receptors, Serotonin (metabolism)
• Serotonin (metabolism)
• Tyrosine 3-Monooxygenase (metabolism)