title: Ghrelin prevents levodopa-induced inhibition of gastric emptying and increases circulating levodopa in fasted rats.
abstract: 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 μg kg(-1)) 10 min before i.p. L-dopa.
  
  
  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 μg 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
  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.
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. lixinw@ucla.edu
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: N P
authors.initials: NP
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Stengel
authors.forename: M
authors.initials: M
authors.lastname: Goebel-Stengel
authors.forename: D H
authors.initials: DH
authors.lastname: St Pierre
authors.forename: N T
authors.initials: NT
authors.lastname: Maidment
authors.forename: Y
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism; D002404:Catheterization; D004298:Dopamine / Q000097:blood; D015259:Dopamine Agents / Q000097:blood / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D054439:Ghrelin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D007980:Levodopa / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015259:Dopamine Agents; D054439:Ghrelin; D007980:Levodopa; D004298:Dopamine