DOPAMINERGIC DEFECT OF ENTERIC NERVOUS-SYSTEM IN PARKINSONS-DISEASE PATIENTS WITH CHRONIC CONSTIPATION

Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine -containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue w as studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neuro ns for dopamine, tyrosine hydroxylase, and vasoactive intestinal polyp eptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene prod uct 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0. 4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subje cts). There was very little difference between the groups in numbers o f tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patien ts had similar distributions of all types of neurons, including dopami nergic myenteric neurons, to the controls. High-performance liquid chr omatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four con trols (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopa mine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunc tion in this disease.