The hydrolysis of striatal adenine- and guanine-based purines in a 6-hydroxydopamine rat model of Parkinson's disease.
Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Jean Pierre
JP
Oses
Cristiane
C
Batassini
Daniela
D
Pochmann
Ana Elisa
AE
Böhmer
Fernanda Cenci
FC
Vuaden
Roberta Bristot
RB
Silvestrin
Alcyr
A
Oliveira
Carla Denise
CD
Bonan
Maurício Reis
MR
Bogo
Diogo Onofre
DO
Souza
Luis Valmor Cruz
LV
Portela
João José de Freitas
JJ
Sarkis
Tadeu
T
Mello e Souza
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism; D000225:Adenine / Q000378:metabolism*; D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D006147:Guanine / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018663:Adrenergic Agents; D007527:Isoenzymes; D010710:Phosphates; D006147:Guanine; D016627:Oxidopamine; D015720:5'-Nucleotidase; D017766:Acid Anhydride Hydrolases; D000225:Adenine