title: 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.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Chenzhe
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hong
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China. Electronic address: llslls1995@163.com.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China. Electronic address: zhu_jx@ccmu.edu.cn.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005769:Gastrointestinal Motility; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D017982:Receptors, Biogenic Amine / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D022702:Receptors, Adrenergic, beta-3; D017982:Receptors, Biogenic Amine; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine