title: Pramipexole protects dopaminergic neurons through paraplegin against 6-hydroxydopamine.
abstract: The neurotransmitter dopamine (DA) regulates various physiological and psychological functions, such as movement, motivation, behavior, and learning. DA exerts its function through DA receptors and a series of studies have reported the role of DAergic receptors in preventing DAergic neuronal degeneration. Here, we studied the DA receptor-mediated neuroprotective effect of the D2-like receptor agonists against 6-hydroxydopamine (6-OHDA)-induced DAergic neurodegeneration. D2-like receptor agonists were administered in the substantia nigra in vivo and to primary cultured neurons. Treatment of 6-OHDA decreased tyrosine hydroxylase (TH) and paraplegin (mitochondrial regulation protein) immunoreactivity, whereas pretreatment with quinpirole (a full D2-like receptor agonist) preserved TH and paraplegin reactivity. This led us to test which DA receptors were necessary for the neuroprotective effect and whether paraplegin can be regulated by D2 or D3 receptor agonists. Pretreatment with the D2 receptor selective agonist, sumanirole, did not preserve TH and paraplegin reactivity from 6-OHDA. However, the D3 receptor agonist, pramipexole, protected TH reactivity and restored paraplegin expression to the control level in the presence of 6-OHDA. Interestingly, pretreatment with the D3 receptor antagonist GR103691 reduced TH and paraplegin expression levels. These results suggest that the D3 receptor agonist may protect DA neurons from the effect of 6-OHDA through the modulation of the mitochondrial regulation protein paraplegin.
authors.affiliation: Department of Veterinary Medicine, Institute of Animal Medicine, Gyeongsang National University, Jinju, South Korea.
authors.forename: Mun Ki
authors.initials: MK
authors.lastname: Kim
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Jea Hyeon
authors.initials: JH
authors.lastname: Cho
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
authors.forename: Chungkil
authors.initials: C
authors.lastname: Won
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; D000077487:Pramipexole; D016627:Oxidopamine; D008666:Metalloendopeptidases; C491813:Spg7 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities