Preventive effect of rikkunshito on gastric motor function inhibited by l-dopa in rats

Abstract

We previously reported that ghrelin prevented l-dopa (LD)-induced inhibition of gastric emptying (GE) of a non-nutrient solution in rats. Parkinson's disease treatment involves the combined administration of l-dopa with the enzyme l-amino acid decarboxylase inhibitor, carbidopa (CD) to reduce peripheral formation of dopamine. We investigated the effect LD/CD given orogastrically (og) on GE of a non-nutrient or nutrient meal and whether og pretreatment with rikkunshito, a kampo medicine clinically used to treat gastroparesis, influenced LD/CD effect on GE and postprandial antral and duodenal motility in conscious rats. LD/CD (20/2mgkg−1) decreased significantly GE to 26.3±6.0% compared to 61.2±3.2% in og vehicle monitored 20-min after a non-nutrient meal and to 41.9±5.8% compared to 72.9±5.2% in og vehicle monitored 60min after a nutrient meal. Rikkunshito (0.5 or 1.0gkg−1) reduced the LD/CD (20/2mgkg−1) inhibition of GE of non-nutrient meal (36.9±7.4% and 46.6±4.8% respectively vs. 12.1±7.4% in og vehicle plus LD/CD) while having no effect alone (56.6±8.5%). The ghrelin antagonist, [d-Lys3]-GHRP-6 (1mgkg−1) injected intraperitoneally partially reversed rikkunshito preventive effect on LD/CD-inhibited GE. Rikkunshito (1.0gkg−1) blocked LD/CD (20/2mgkg−1)-induced delayed GE of a nutrient meal and the reduction of postprandial antral motility. In 6-hydroxydopamine-induced Parkinson's disease rat model, rikkunshito (1.0gkg−1, og) also prevented LD/CD-inhibited gastric emptying of a nutrient meal and enhanced fasting plasma levels of acylated ghrelin. These data indicate that oral rikkunshito alleviates the delayed GE induced by LD/CD in naïve and PD rat model in part through ghrelin-related mechanisms.