Atrial Natriuretic peptide stimulates dopamine tubular transport by organic cation transporters: A novel mechanism to enhance renal sodium excretion.

KRAVETZ MC; DEL MAURO JS; TOBLLI JE.; KOUYOUMDZIAN NM; LEE BM; PANDOLFO M; FERNÁNDEZ B.E; RUKAVINA MIKUSIC NL; CARRANZA A; GIRONACCI MM; CHOI MR; KRAVETZ MC; DEL MAURO JS; TOBLLI JE.; KOUYOUMDZIAN NM; LEE BM; PANDOLFO M; FERNÁNDEZ B.E; RUKAVINA MIKUSIC NL; CARRANZA A; GIRONACCI MM; CHOI MR

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016 vol. 11 p. 1 - 17

1932-6203

AbstractThe aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) onorganic cation transporters (OCTs) expression and activity, and its consequences on dopamineurinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley ratswere infused with isotonic saline solution during 120 minutes and randomized in nine differentgroups: 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 determinedand urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by westernblot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renaluptake was determined in vitro. Compared to P+T group, ANP and dopamine infusionincreased diuresis, urinary sodium and dopamine excretion significantly. These effectswere more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstratingthat 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 inthe same experimental groups. Although OCTs and D1-receptor protein expression werenot modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANPthrough activation of NPR-A receptor and protein kinase G as signaling pathway. This effectwas reflected by an increase in urinary dopamine excretion, natriuresis, diuresis anddecreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity ofANP and dopamine together in a common mechanism to enhance their natriuretic anddiuretic effects.