Impairment of the neuronal dopamine transporter activity in MPP(+)-treated rat was not prevented by treatments with nitric oxide synthase or poly(ADP-ribose) polymerase inhibitors.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite MPP(+), damages of the nigrostriatal dopaminergic pathway, similar to those observed in Parkinson's disease. An intranigral injection of 10 microg MPP(+) in rat induced a decrease of about 30% of the neuronal dopamine transporter (DAT) activity 21 days after lesion. Based on the hypothesis that MPTP/MPP(+) neurotoxicity involves the nitric oxide (NO) production and/or an activation of poly(ADP-ribose) polymerase (PARP), we investigated the preventive effects of a treatment either with L-Name, a NO synthase (NOS) inhibitor or 3-aminobenzamide, a PARP inhibitor on the reduction of dopamine uptake induced by MPP(+). Rats received a daily injection i.p. of 50 mg/kg L-Name or 10 mg/kg 3-aminobenzamide 3 days before and during 21 days after the MPP(+) lesion. The results showed that inhibitors of NOS and PARP did not prevent the alteration of DAT activity induced by 10 microg MPP(+), indicating that NO and PARP were not involved in the biochemical cascade leading to the inhibition of rat DAT activity by MPP(+) in our experimental conditions.
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Groupe d'Etudes des Mécanismes Cellulaires de l'Ischémie GEMCI, UPRES EA 1223, 34, rue du Jardin des Plantes, BP 199, 86005 Poitiers cedex, France. guylene.page@univ-poitiers.fr
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D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C493216:Slc6a3 protein, rat; D014316:Tritium; D011064:Poly Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine