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MPTP处理的患有膀胱反射亢进的普通狨猴逼尿肌收缩力改变。

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia.

作者信息

Pritchard Sara, Jackson Michael J, Hikima Atsuko, Lione Lisa, Benham Christopher D, Chaudhuri K Ray, Rose Sarah, Jenner Peter, Iravani Mahmoud M

机构信息

Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, Hatfield, United Kingdom.

Neurodegenerative Disease Research Group, Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

出版信息

PLoS One. 2017 May 17;12(5):e0175797. doi: 10.1371/journal.pone.0175797. eCollection 2017.

Abstract

Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus). However, the neurogenic contractions following electrical field stimulation of the intrinsic nerves (EFS) were markedly greater in strips obtained from MPTP treated animals. EFS evoked non-cholinergic contractions following atropine were also greater but the contribution of the cholinergic innervation as a proportion of the overall contraction was smaller in the detrusor strips of MPTP treated animals, suggesting a preferential enhancement of the non-cholinergic transmission. Although dopaminergic mechanism has been proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact bladder, the present data indicates that the increased neurogenically mediated contractions where no extrinsic innervation exists might be due to long-term adaptive changes locally as a result of the loss of the nigrostriatal output.

摘要

膀胱反射亢进是帕金森病常见的非运动特征。我们现在报告缺乏神经输入的分离灵长类逼尿肌条的收缩性,并表明在给予MPTP后,自发收缩的幅度和频率增加。这些反应分别不受多巴胺D1和D2受体激动剂A77636和罗匹尼罗的影响。外源性卡巴胆碱、组胺或ATP引起的收缩相似,在从正常和MPTP处理的普通狨猴(绢毛猴)获得的逼尿肌条中,去甲肾上腺素诱导的舒张幅度没有差异。然而,在从MPTP处理的动物获得的条带中,电场刺激内在神经(EFS)后的神经源性收缩明显更大。阿托品后EFS诱发的非胆碱能收缩也更大,但在MPTP处理动物的逼尿肌条中,胆碱能神经支配作为总收缩比例的贡献较小,表明非胆碱能传递优先增强。尽管有人提出多巴胺能机制是MPTP处理的膀胱完整动物膀胱反射亢进的基础,但目前的数据表明,在不存在外在神经支配的情况下,神经源性介导的收缩增加可能是由于黑质纹状体输出丧失导致的局部长期适应性变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/5435136/b0b584f53be4/pone.0175797.g001.jpg

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