title: Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion.
abstract: The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects.
authors.affiliation: Cardiological Research Institute, National Scientific and Technical Research Council, Buenos Aires, Argentina.|Pathophysiology and Clinical Biochemistry Institute, Buenos Aires, Argentina.
authors.forename: Nicolás M
authors.initials: NM
authors.lastname: Kouyoumdzian
authors.affiliation: Cardiological Research Institute, National Scientific and Technical Research Council, Buenos Aires, Argentina.|Pathophysiology and Clinical Biochemistry Institute, Buenos Aires, Argentina.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Rukavina Mikusic
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Kravetz
authors.affiliation: Department of General Surgery, Johns Hopkins Hospital, Baltimore, Maryland, United States of America.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carranza
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Julieta S
authors.initials: JS
authors.lastname: Del Mauro
authors.affiliation: Pathophysiology and Clinical Biochemistry Institute, Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pandolfo
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mariela M
authors.initials: MM
authors.lastname: Gironacci
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Gorzalczany
authors.affiliation: Cardiological Research Institute, National Scientific and Technical Research Council, Buenos Aires, Argentina.|Deutsch Hospital, Buenos Aires, Argentina.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: Cardiological Research Institute, National Scientific and Technical Research Council, Buenos Aires, Argentina.|Pathophysiology and Clinical Biochemistry Institute, Buenos Aires, Argentina.
authors.forename: Belisario E
authors.initials: BE
authors.lastname: Fernández
authors.affiliation: Cardiological Research Institute, National Scientific and Technical Research Council, Buenos Aires, Argentina.|Pathophysiology and Clinical Biochemistry Institute, Buenos Aires, Argentina.|Department of Anatomy and Histology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Marcelo R
authors.identifier: http://orcid.org/0000-0003-2909-8534
authors.initials: MR
authors.lastname: Choi
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D009320:Atrial Natriuretic Factor; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine