Atrial natriuretic peptide stimulates dopamine tubular transport by organic cation transporters: a novel mechanism to enhance renal sodium excretion

KOUYOUMDZIAN NM; RUKAVINA MIKUSIC NL; KRAVETZ MC; LEE BM; CARRANZA A; HOCHT C; PANDOLFO M; GIRONACCI MM; GORZALCZANY S; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

PLOS ONE

PUBLIC LIBRARY SCIENCE

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

1932-6203

The aim of this studywas to demonstrate the effects of atrial natriuretic peptide (ANP) on organiccation transporters (OCTs) expression and activity, and its consequences ondopamine urinary levels, Na+, K+-ATPase activity andrenal function. Male Sprague Dawley rats were infused with isotonic salinesolution 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+DAand ANP+DA+D-22. Renal functional parameters were determined and urinarydopamine concentration was quantified by HPLC. Expression of OCTs andD1-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-DArenal uptake was determined in vitro. Compared to P+T group, ANP anddopamine infusion increased diuresis, urinary sodium and dopamine excretionsignificantly. These effects were more pronounced in ANP+DA group and reversedby OCTs blockade by D-22, demonstrating that OCTs are implied in ANPstimulated-DA uptake and transport in renal tissues. The activity of Na+,K+-ATPase exhibited a similar fashion when it was measured in thesame experimental groups. Although OCTs and D1-receptor protein expression werenot modified by ANP, OCTs-dependent-dopamine tubular uptake was increased byANP through activation of NPR-A receptor and protein kinase G as signalingpathway. This effect was reflected by an increase in urinary dopamineexcretion, natriuresis, diuresis and decreased Na+, K+-ATPaseactivity. OCTs represent a novel target that links the activity of ANP anddopamine together in a common mechanism to enhance their natriuretic anddiuretic effects.