title: 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 (20/2 mgkg(-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-Lys(3)]-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.
authors.affiliation: 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. Electronic address: lixinw@ucla.edu.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tsumura Research Laboratories, Ibaraki, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Mogami
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Karasawa
authors.affiliation: Tsumura Research Laboratories, Ibaraki, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamada
authors.affiliation: 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.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yakabi
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
authors.affiliation: Tsumura Research Laboratories, Ibaraki, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.affiliation: 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.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D054439:Ghrelin / Q000097:blood; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D019518:Postprandial Period; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors
chemical_list: D004365:Drugs, Chinese Herbal; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C084136:liu-jun-zi-tang; D007980:Levodopa; D002230:Carbidopa
keywords: Gastric motility; Ghrelin; Parkinson's disease; Rats; Rikkunshito; l-dopa