Bowel dysfunction is a common non-motor symptom in Parkinson’s disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction. While NO-synthase inhibitor L-NAME concentration dependently augmented the neurogenically-evoked contractions and inhibited the relaxations in normal tissues, it had no effects on the MPTP ileum. Immunohistochemical analyses of the myenteric plexus showed that ChAT-immunoreactivity (-ir) was significantly reduced and the density of the enteric glial cells as shown by SOX-10-ir was increased. However, no change in TH-, 5-HT-, VIP- or nNOS-ir was observed in the MPTP tissues. The enhancement of the neurogenically-evoked contractions and the inhibition of the relaxation phase by L-NAME in the control tissues is in line with NO’s direct relaxing effect on smooth muscle and its indirect inhibitory effect on ACh release. The absence of the relaxation and the inefficacy of L-NAME in the MPTP tissues suggests that central dopaminergic loss dopamine may eventually lead to the impairment of NO signal coupling that affects bowel function, and this may be the result of a complex dysregulation at the level of the neuroeffector junction.

肠功能障碍是帕金森氏病（PD）的常见非运动症状。胃肠道中主要的收缩性神经递质是乙酰胆碱（ACh），而一氧化氮（NO）除了调节ACh释放外，还引起平滑肌的松弛。这项研究的目的是表征1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的mar猴的分离回肠中的功能和神经化学变化，mar猴是PD运动功能障碍的既定模型。虽然NO合酶抑制剂L-NAME的浓度依赖性地增加了神经诱发的收缩并抑制了正常组织的松弛，但它对MPTP回肠没有影响。对肌间神经丛的免疫组织化学分析表明，ChAT免疫反应性（-ir）显着降低，而SOX-10-ir显示的肠神经胶质细胞密度增加。然而，在MPTP组织中未观察到TH-，5-HT-，VIP-或nNOS-ir的变化。对照组织中神经源性诱发的收缩的增强和L-NAME对松弛相的抑制与NO对平滑肌的直接松弛作用及其对ACh释放的间接抑制作用相一致。MPTP组织中缺乏松弛和L-NAME无效，表明中枢多巴胺能损失多巴胺可能最终导致影响肠道功能的NO信号偶联受损，这可能是该水平复杂失调的结果神经效应交界处。然而，在MPTP组织中未观察到TH-，5-HT-，VIP-或nNOS-ir的变化。对照组织中神经源性诱发的收缩的增强和L-NAME对松弛相的抑制与NO对平滑肌的直接松弛作用及其对ACh释放的间接抑制作用相一致。MPTP组织中缺乏松弛和L-NAME无效，表明中枢多巴胺能损失多巴胺可能最终导致影响肠道功能的NO信号偶联受损，这可能是该水平复杂失调的结果神经效应交界处。然而，在MPTP组织中未观察到TH-，5-HT-，VIP-或nNOS-ir的变化。对照组织中神经源性诱发的收缩的增强和L-NAME对松弛相的抑制与NO对平滑肌的直接松弛作用及其对ACh释放的间接抑制作用相一致。MPTP组织中缺乏松弛和L-NAME无效，表明中枢多巴胺能损失多巴胺可能最终导致影响肠道功能的NO信号偶联受损，这可能是该水平复杂失调的结果神经效应交界处。对照组织中神经源性诱发的收缩的增强和L-NAME对松弛相的抑制与NO对平滑肌的直接松弛作用及其对ACh释放的间接抑制作用相一致。MPTP组织中缺乏松弛和L-NAME无效，表明中枢多巴胺能损失多巴胺可能最终导致影响肠道功能的NO信号偶联受损，这可能是该水平复杂失调的结果神经效应交界处。对照组织中神经源性诱发的收缩的增强和L-NAME对松弛相的抑制与NO对平滑肌的直接松弛作用及其对ACh释放的间接抑制作用相一致。MPTP组织中缺乏松弛和L-NAME无效，表明中枢多巴胺能损失多巴胺可能最终导致影响肠道功能的NO信号偶联受损，这可能是该水平复杂失调的结果神经效应交界处。