INVESTIGADORES
CHOI Marcelo Roberto
artículos
Título:
Signaling Pathways involved in Atrial Natriuretic Factor and Dopamine regulation of renal Na+, K+-ATPase activity
Autor/es:
CORREA AH; CHOI MR; GIRONACCI MM; VALERA MS; FERNÁNDEZ BE
Revista:
REGULATORY PEPTIDES
Editorial:
Elsevier
Referencias:
Lugar: Amsterdam; Año: 2007 vol. 138 p. 26 - 31
ISSN:
0167-0115
Resumen:
Dopamine (DA) and atrial natriuretic factor (ANF) share a number of
physiological effects. We hypothesized that ANF and the renal dopaminergic
system could interact and enhance the natriuretic and diuretic effects of the
peptide. We have previously reported that the ANF-stimulated DA uptake in renal
tubular cells is mediated by the natriuretic peptide type-A receptor (NPR-A). Our
aim was to investigate the signaling pathways that mediate ANF effects on renal
3 H-DA uptake. Methylene blue (10 µM), an unspecific inhibitor of guanylate
cyclase (GC), blunted ANF elicited increase of DA uptake. ODQ (10 µM) a
specific inhibitor of soluble GC, did not modify DA uptake and did not reverse
ANF-induced increase of DA uptake; then the participation of nitric oxide
dependent pathways must be discarded. The second messenger was the cGMP
since the analogous 125 µM 8Br-cGMP mimicked ANF effects: The specific
inhibitor of the proteinkinase G (PKG), KT 5823 (1 µM) blocked ANF effects
indicating that PKG is involved. We examined if ANF effects on DA uptake
were able to modify Na + , K + -adenosine triphosphatase (Na + , K + -ATPase)
activity. The experiments were designed by means of inhibition of renal DA
synthesis by carbidopa and neuronal DA uptake blocked by nomifensine. In
these conditions renal Na + , K + -ATPase activity was increased, in agreement
with the decrease of DA availability. When in similar conditions, exogenous
DA was added to the incubation medium, the activity of the enzyme tended to
decrease, following to the restored availability of DA. The addition of ANF
alone had similar effects to the addition of DA on the sodium pump, but when
both were added together, the activity of Na + , K + -ATPase was decreased.
In conclusion, ANF stimulates extraneuronal DA uptake in external
cortex tissues by activation of NPR-A receptors coupled to GC and it signals
through cGMP as second messenger and PKG. Dopamine and ANF may
achieve their effects through a common pathway that involves reversible
deactivation of renal tubular Na + , K + -ATPase activity. This mechanism
demonstrates a DA-ANF relationship involved in the modulation of both
decreased sodium reabsorption and increased natriuresis.