title: Response of colonic motility to dopaminergic stimulation is subverted in rats with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in Parkinson's disease.
abstract: BACKGROUND
  Constipation is extremely common in patients with Parkinson's disease (PD) and has been described in PD animal models. In this study, we investigated whether a PD-like degeneration of dopaminergic neurons of the substantia nigra can influence peristalsis in colonic segments of rats by impacting on enteric dopaminergic transmission.
  
  
  METHODS
  Male, Sprague-Dawley rats received a unilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA), or saline, into the medial-forebrain-bundle. Peristaltic activity was recorded in isolated colonic segments, in baseline conditions and following exposure to combinations of D2 receptor (DRD2) agonist sumanirole and antagonist L-741626. Dopamine levels and DRD2 expression were assessed in the ileum and colon of animals. We also investigated the involvement of the dorsal motor nucleus of the vagus (DMV) - a potential relay station between central dopaminergic denervation and gastrointestinal (GI) dysfunction - by analyzing cytochrome c oxidase activity and FosB/DeltaFosB expression in DMV neurons.
  
  
  RESULTS
  We observed profound alterations in the response of colonic segments of 6-OHDA lesioned animals to DRD2 stimulation. In fact, the inhibition of colonic peristalsis elicited by sumanirole in control rats was absent in 6-OHDA-lesioned animals. These animals also showed reduced DRD2 expression in the colon, along with elevation of dopamine levels. No significant changes were detected within the DMV.
  
  
  CONCLUSIONS
  Our results demonstrate that selective lesion of the nigrostriatal dopaminergic pathway subverts the physiological response of the colon to dopaminergic stimulation, opening new perspectives in the comprehension and treatment of GI dysfunctions associated with PD.
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Levandis
authors.affiliation: Dept. of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Balestra
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Siani
authors.affiliation: Department of Molecular Medicine, IRCCS San Matteo Foundation, University of Pavia, Pavia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Rizzo
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ghezzi
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ambrosi
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cerri
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonizzi
authors.affiliation: Dept. of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Vicini
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vairetti
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferrigno
authors.affiliation: Dept. of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Pastoris
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino", National Neurological Institute, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Blandini
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D003248:Constipation / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008297:Male; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries*
chemical_list: C000607792:DRD2 protein, rat; D017448:Receptors, Dopamine D2; D016627:Oxidopamine
keywords: 6-OHDA; Parkinson's disease; dopamine D2 receptor; dorsal motor nucleus of the vagus nerve; peristalsis