Abstract
Parkinson's disease, PD, a progressive neurodegenerative disorder characterized by extrapyramidal symptoms, is often associated with non-motor symptoms. Though constipation appears most frequently among these symptoms, the mechanism of constipation in PD has not been clarified and an appropriate treatment method has not been established. Intestinal motility is regulated by extrinsic autonomic nerves, the enteric nervous system (ENS) and the interstitial cells of Cajal. Of these forms of regulation, we have been focusing attention on the dopaminergic nervous system in ENS to investigate its involvement in constipation of PD model rats. It is known that dopamine has an inhibitory effect on intestinal movement through dopamine receptor D2, D2R. We have already reported that the colon of PD model rats has an enhanced sensitivity to dopamine, and this can be due to an increase in D2R. In this study, we have investigated the sensitivity of the small intestine to dopamine, and examined the effectiveness of domperidone, a D2R antagonist, against constipation in PD model rats. We administered apomorphine, a dopamine receptor agonist, and recorded contraction movement of the isolated small intestine in Krebs solution; the motility of the intestinal tract of the PD model rats was significantly suppressed for a period longer than that of the control rats. Next, when domperidone was administered to the PD model rats, the decline in the food transportation speed in the small intestine was improved, and fecal weight was significantly increased. These results suggested that the small intestinal tract of the PD rat became more sensitive to dopamine similar to the colon, which indicated the influence on the movement of the intestinal tract, and that the D2R antagonist was effective for constipation in PD.
