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Renalase regulates peripheral and central dopaminergic activities

Title
Renalase regulates peripheral and central dopaminergic activities
Type
Article in International Scientific Journal
Year
2015
Authors
Quelhas Santos, J
(Author)
FMUP
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Serrao, MP
(Author)
Other
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Soares Silva, I
(Author)
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Fernandes Cerqueira, C
(Author)
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Simoes Silva, L
(Author)
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Pinho, MJ
(Author)
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Remiao, F
(Author)
FFUP
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Sampaio Maia, B
(Author)
FMUP
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Desir, GV
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Pestana, M
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Journal
Vol. 308
Pages: F84-F91
ISSN: 1931-857X
Indexing
Publicação em ISI Web of Science ISI Web of Science
Pubmed / Medline
Scientific classification
CORDIS: Health sciences
Other information
Authenticus ID: P-00A-45Z
Abstract (EN): Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-L-3,4-dihydroxyphenylalanine (L-DOPA) ratios without changes in renal tubular aromatic-L-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and L-DOPA as well as in urinary excretion of Epi, DA, and DA-to-L-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced L-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 8
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