Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The hydrolysis of striatal adenine- and guanine-based purines in a 6-hydroxydopamine rat model of Parkinson's disease. 2104 37

Ethanol is a widely consumed drug that acts on the central nervous system (CNS), modifying several signal transduction pathways activated by hormones and neurotransmitters. The zebrafish is an experimental model for the study of human diseases and the use of this species in biochemical and behavioral studies on alcoholism and alcohol-dependence has increased recently. However, there are no data concerning the effects of chronic ethanol exposure on the purinergic system, where extracellular nucleotides act as signaling molecules. Purinergic signaling is controlled by a group of enzymes named ectonucleotidases, which include NTPDases and ecto-5'-nucleotidase already characterized in zebrafish brain. The aim of this study was to evaluate nucleotide hydrolysis by NTPDases and ecto-5'-nucleotidase after long-term ethanol exposure. Additionally, the gene expression patterns of NTPDases1-3 and 5'-nucleotidase were determined. Animals were exposed to 0.5% ethanol for 7, 14, and 28 days. There were no significant changes in ATP and GTP hydrolysis after all treatments. However, a decrease in ADP (46% and 34%) and GDP (48% and 36%) hydrolysis was verified after 7 and 14 days, respectively. After 7 and 14 days of ethanol exposure, a significant decrease in AMP hydrolysis (48% and 36%) was also observed, whereas GMP hydrolysis was inhibited only after 7 days (46%). NTPDase2_mv and NTPDase3 mRNA transcript levels decreased after 7 and 14 days, respectively. In contrast, ethanol increased NTPDase1, NTPDase2_mq, and NTPDase3 transcript levels after 28 days of exposure. NTPDase2_mg and 5'-nucleotidase gene expression was not altered. Therefore, the ectonucleotidase pathway may be a target of chronic ethanol toxicity and the regulation of purinergic system could play a key role in the neurochemical mechanisms underlying the effects of ethanol on the CNS.
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PMID:Chronic ethanol treatment alters purine nucleotide hydrolysis and nucleotidase gene expression pattern in zebrafish brain. 2170 70


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