Ghrelin prevents levodopa‐induced inhibition of gastric emptying and increases circulating levodopa in fasted rats

Wang, L.; Murphy, Niall P.; Stengel, Andreas; Goebel-Stengel, Miriam; St.-Pierre, David H.; Maidment, Nigel T.; Taché, Yvette

doi:10.1111/j.1365-2982.2012.01904.x

Cited by 22 publications

(28 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The oral administration of l -dopa/carbidopa (LD/CD) given in the fasting state or before a low protein meal inhibits gastric emptying in healthy young or elderly volunteers [40–42,57] as well as in PD patients who have already developed delayed solid gastric emptying [12,19,24]. In contrast to clinical studies, there is a paucity of experimental studies on the effects of l -dopa on gastric motor function [53,60] and the influence of peripheral AADC inhibitors administered orally in conjunction with l -dopa is still unknown in rodents.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This is largely due to the fact that the low quantities of X/A-like cells hamper the enrichment to pure cell preparations and immortalized ghrelin producing MGN3-1 tumor cell lines [53] only allow a limited proportion of extrapolation to native X/A-like cells. This was recently shown by the demonstration that dopamine stimulates ghrelin release from MGN3-1 cells [54], while in vivo increased levels of dopamine in the circulation [55] or in the gastric mucosa [56] did not alter fasting ghrelin levels in rats. Animal models with fluorescent dye coupled to the ghrelin promoter allow to enrich ghrelin producing cells to higher purity as in the recent use of green fluorescent dye [57•• ].…”

Section: Regulation Of Peptide Releasementioning

confidence: 98%

Gastric Peptides and their Regulation of Hunger and Satiety

Stengel

Taché

2012

Curr Gastroenterol Rep

View full text Add to dashboard Cite

Ingestion of food affects the secretion of hormones from specialized endocrine cells scattered within the intestinal mucosa. Upon release, these hormones mostly decrease food intake by signaling information to the brain. Although enteroendocrine cells in the small intestine were thought to represent the predominant gut-brain regulators of food intake, recent advances also established a major role for gastric hormones in these regulatory pathways. First and foremost, the gastric endocrine X/A-like cell was in the focus of many studies due to the production of ghrelin which is until now the only known orexigenic hormone that is peripherally produced and centrally acting. Although X/A-cells were initially thought to only release one hormone that stimulates food intake, this view has changed with the identification of additional peptide products also derived from this cell, namely desacyl ghrelin, obestatin and nesfatin-1. Desacyl ghrelin may play a counter-regulatory role to the food intake stimulatory effect of ghrelin. The same property was suggested for obestatin; however, this hypothesis could not be confirmed in numerous subsequent studies. Moreover, the description of the stomach as the major source of the novel anorexigenic hormone nesfatin-1 derived from the NUCB2 gene further corroborated the assumption that the gastric X/A-like cell is not only a stimulator but also an inhibitor of feeding thereby acting as so far unique dual regulator of food intake located in a logistically important place where the gastrointestinal tract has initial contact with food.

show abstract

“…It is well known that serum ghrelin levels correlate with appetite and GET [13]. Wang et al [14] suggested that ghrelin prevents L -dopa-induced delayed gastric emptying in a rat model. To our knowledge, our results are the first to demonstrate a difference in serum ghrelin levels between normal-GET and delayed-GET groups of PD patients.…”

Section: Discussionmentioning

confidence: 99%

“…One likely candidate for this regulation is ghrelin, which exhibits prokinetic effects and centrally enhances the appetite [13]. Recently, Wang et al [14] reported that ghrelin prevented L -dopa-induced delayed gastric emptying in a rodent model. …”

Section: Introductionmentioning

confidence: 99%

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease

Kwon

Jo²,

Lee³

et al. 2016

Neurodegener Dis

View full text Add to dashboard Cite

Background and Objectives: Gastrointestinal dysfunction is a common non motor symptom in Parkinson's disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. Methods: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T_1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group. Results: The serum 25-hydroxyvitamin D₃ levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D₃ level was independently associated with delayed gastric emptying in PD patients. Conclusions: Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD.

show abstract

Ghrelin prevents levodopa‐induced inhibition of gastric emptying and increases circulating levodopa in fasted rats

Cited by 22 publications

References 70 publications

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

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

Gastric Peptides and their Regulation of Hunger and Satiety

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease

Contact Info

Product

Resources

About