Preventive effect of rikkunshito on gastric motor function inhibited by l-dopa in rats |
| |
| Institution: | 1. CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, CA, USA;2. Tsumura Research Laboratories, Ibaraki, Japan;3. Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan;1. Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France;2. Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France;1. Vírgen del Rocío University Hospital, Research Laboratory on Neuropeptides Sevilla, Spain;2. Hospital Juan Ramón Jiménez, Huelva, Spain;3. Deparment of Pathology, “Vírgen del Rocío” University Hospital, Sevilla, Spain;4. Institute of Neurosciences of Castilla y León (INCYL) , Laboratory of Neuroanatomy of the Peptidergic Systems, Laboratory 14, Salamanca, Spain;1. Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, United States;2. School of Medicine, Wayne State University, Detroit, MI 48202, United States;1. CNR Institute of Clinical Physiology, Laboratory of Cardiovascular Biochemistry, Pisa, Italy;2. CNR Institute of Clinical Physiology, Milan, Italy;3. Cardiovascular Department, Niguarda Ca’ Granda Hospital, Milan, Italy;1. Department of Chemistry, The University of Adelaide, South Australia 5005, Australia;2. School of Chemistry, Bio21 Institute, University of Melbourne, Victoria 3010, Australia |
| |
| 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 (20/2 mg kg−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 60 min after a nutrient meal. Rikkunshito (0.5 or 1.0 g kg−1) reduced the LD/CD (20/2 mg kg−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 (1 mg kg−1) injected intraperitoneally partially reversed rikkunshito preventive effect on LD/CD-inhibited GE. Rikkunshito (1.0 g kg−1) blocked LD/CD (20/2 mg kg−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 (1.0 g kg−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. |
| |
| Keywords: | Gastric motility Ghrelin Parkinson's disease Rats Rikkunshito |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
