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Ghrelin prevents levodopa‐induced inhibition of gastric emptying and increases circulating levodopa in fasted rats
Author(s) -
Wang L.,
Murphy N. P.,
Stengel A.,
GoebelStengel M.,
Pierre D. H. St,
Maidment N. T.,
Taché Y.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2012.01904.x
Subject(s) - levodopa , ghrelin , gastric emptying , endocrinology , medicine , dopamine , chemistry , radioimmunoassay , stomach , parkinson's disease , hormone , disease
Background Levodopa ( l ‐dopa) is the most commonly used treatment for alleviating symptoms of Parkinson’s disease. However, l ‐dopa delays gastric emptying, which dampens its absorption. We investigated whether ghrelin prevents l ‐dopa action on gastric emptying and enhances circulating l ‐dopa in rats. Methods Gastric emptying of non‐nutrient methylcellulose/phenol red viscous solution was determined in fasted rats treated with orogastric or intraperitoneal (i.p.) l ‐dopa, or intravenous (i.v.) ghrelin 10 min before orogastric l ‐dopa. Plasma l ‐dopa and dopamine levels were determined by high pressure liquid chromatography. Plasma acyl ghrelin levels were assessed by radioimmunoassay. Fos expression in the brain was immunostained after i.v. ghrelin (30 μ g kg −1 ) 10 min before i.p. l ‐dopa. Key Results Levodopa (5 and 15 mg kg −1 ) decreased significantly gastric emptying by 32% and 62%, respectively, when administered orally, and by 91% and 83% when injected i.p. Ghrelin (30 or 100 μ g kg −1 , i.v.) completely prevented l ‐dopa’s (15 mg kg −1 , orogastrically) inhibitory action on gastric emptying and enhanced plasma l ‐dopa and dopamine levels compared with vehicle 15 min after orogastric l ‐dopa. Levodopa (5 mg kg −1 ) did not modify plasma acyl ghrelin levels at 30 min, 1, and 2 h after i.v. injection. Levodopa (15 mg kg −1 , i.p.) induced Fos in brain autonomic centers, which was not modified by i.v. ghrelin. Conclusions & Inferences Ghrelin counteracts l ‐dopa‐induced delayed gastric emptying but not Fos induction in the brain and enhances circulating l ‐dopa levels. Potential therapeutic benefits of ghrelin agonists in Parkinson’s disease patients treated with l ‐dopa remain to be investigated.