title: Renalase regulates peripheral and central dopaminergic activities.
abstract: 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.
authors.affiliation: Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal; Nephrology and Infectious Diseases Research and Development Group, Instituto Nacional de Engenharia Biomédica-(I3S); sjanete@med.up.pt.
authors.forename: Janete
authors.initials: J
authors.lastname: Quelhas-Santos
authors.affiliation: Faculdade de Medicina da Universidade do Porto, Department of Pharmacology and Therapeutics, Porto, Portugal;
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Serrão
authors.affiliation: Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal; Nephrology and Infectious Diseases Research and Development Group, Instituto Nacional de Engenharia Biomédica-(I3S);
authors.forename: Isabel
authors.initials: I
authors.lastname: Soares-Silva
authors.affiliation: Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal;
authors.forename: Cátia
authors.initials: C
authors.lastname: Fernandes-Cerqueira
authors.affiliation: Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal;
authors.forename: Liliana
authors.initials: L
authors.lastname: Simões-Silva
authors.affiliation: Faculdade de Medicina da Universidade do Porto, Department of Pharmacology and Therapeutics, Porto, Portugal;
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pinho
authors.affiliation: Centro de Química da Universidade do Porto/Serviço de Toxicologia, Faculdade de Farmácia, University of Porto, Porto, Portugal;
authors.forename: Fernando
authors.initials: F
authors.lastname: Remião
authors.affiliation: Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal; Faculty of Dental Medicine, University of Porto, Porto, Portugal;
authors.forename: Benedita
authors.initials: B
authors.lastname: Sampaio-Maia
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcree System, Yale University, New Haven, Connecticut;
authors.forename: Gary V
authors.initials: GV
authors.lastname: Desir
authors.affiliation: Nephrology and Infectious Diseases Research and Development Group, Instituto Nacional de Engenharia Biomédica-(I3S); Faculdade de Medicina da Universidade do Porto, Department of Renal, Urological, and Infectious Diseases, Porto, Portugal; and Department of Nephrology, São João Hospital Center, Entidade Pública Empresarial, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pestana
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000097:blood* / Q000652:urine*; D059290:Dopaminergic Neurons / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D008995:Monoamine Oxidase; C521557:renalase; D004298:Dopamine
keywords: epinephrine; knockout mouse model; l-3,4-dihydroxyphenylalanine; renal dopamine