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Reduced acetylcholine and elevated muscarinic receptor 2 in duodenal mucosa contribute to the impairment of mucus secretion in 6-hydroxydopamine-induced Parkinson’s disease rats

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Abstract

Patients with Parkinson’s disease (PD) have a higher incidence rate of duodenal ulcers. The mucus barrier provides the first line of defense for duodenal mucosal protection. However, it is unknown whether duodenal mucus secretion is affected in PD. In the present study, we used the rats microinjected 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra to investigate duodenal mucus secretion and potential therapeutic targets in duodenal ulcer in PD. Alcian blue-periodic acid-Schiff, transmission electron microscopy, immunofluorescence, duodenal mucosal incubation, and enzyme-linked immunosorbent assays were used. The 6-OHDA rats exhibited mucin accumulation and retention in duodenal goblet cells. Mucin granules were unable to fuse with the apical membranes of goblet cells, and the exocytosis ratio of goblet cells was significantly reduced. Moreover, decreased acetylcholine and increased muscarinic receptor 2 (M2R) levels were detected in the duodenal mucosa of 6-OHDA rats. Bilateral vagotomy rats were also characterized by defective duodenal mucus secretion and decreased acetylcholine with increased M2R levels in the duodenal mucosa. Application of the cholinomimetic drug carbachol or blocking M2R with methoctramine significantly promoted mucus secretion by goblet cells and increased MUC2 content in duodenal mucosa-incubated solutions from 6-OHDA and vagotomy rats. We conclude that the reduced acetylcholine and increased M2R contribute to the impaired duodenal mucus secretion of 6-OHDA rats. The study provides new insights into the mechanism of duodenal mucus secretion and potential therapeutic targets for the treatment of duodenal ulcers in PD patients.

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Funding

This work was financially supported through grants from the National Key Research and Development Program (2016YFC1302203), the National Natural Science Foundation of China (31871159, 32071126 and 81570695), the Beijing Nature Science Foundation (7182014 and 5172006), and the Scientific Research Common Program of Beijing Municipal Commission of Education (KM202010025030).

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China

    Jing-Ting Yan, Xiao-Yu Liu, Guang-Wen Li, Li-Fei Zheng, Xiao-Li Zhang, Yue Zhang, Xiao-Yan Feng & Jin-Xia Zhu

  2. Grade 2017 Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, China

    Jing-Hua Liu

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  1. Jing-Ting Yan
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Jin-Xia Zhu and Xiao-Yan Feng designed the research project; Jing-Ting Yan, Xiao-Yu Liu, and Guang-Wen Li performed the experiments; Li-Fei Zheng, Xiao-Li Zhang, and Yue Zhang provided technical support; Jing-Hua Liu produced Fig. 5; Jing-Ting Yan wrote the manuscript; and Xiao-Yan Feng and Jin-Xia Zhu revised the manuscript.

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Correspondence to Xiao-Yan Feng or Jin-Xia Zhu.

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Yan, JT., Liu, XY., Liu, JH. et al. Reduced acetylcholine and elevated muscarinic receptor 2 in duodenal mucosa contribute to the impairment of mucus secretion in 6-hydroxydopamine-induced Parkinson’s disease rats. Cell Tissue Res 386, 249–260 (2021). https://doi.org/10.1007/s00441-021-03515-7

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