Signaling pathways involved in atrial natriuretic factor and dopamine regulation of renal Na+, K+-ATPase activity.

AH CORREA, M CHOI, MM GIRONACCI, MS VALERA, BE FERNANDEZ

REGULATORY PEPTIDES

Elsevier

Año: 2007 vol. 138 p. 26 - 31

0167-0115

Dopamine (DA) and atrial natriuretic factor (ANF) share a number of physiological effects.We hypothesized that ANF and the renal dopaminergicsystem could interact and enhance the natriuretic and diuretic effects of the peptide.We have previously reported that the ANF-stimulated DA uptakein renal tubular cells is mediated by the natriuretic peptide type-A receptor (NPR-A). Our aim was to investigate the signaling pathways that mediateANF effects on renal 3H-DA uptake. Methylene blue (10 μM), an unspecific inhibitor of guanylate cyclase (GC), blunted ANF elicited increase ofDAuptake.ODQ (10 μM) a specific inhibitor of soluble GC, did not modify DA uptake and did not reverse ANF-induced increase ofDA uptake; then theparticipation of nitric oxide-dependent pathways must be discarded. The second messenger was the cGMP since the analogous 125 μM8-Br-cGMPmimicked ANF effects. The specific inhibitor of the protein kinase 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 weredesigned 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 DAwas added to theincubation medium, the activity of the enzyme tended to decrease, following to the restored availability of DA. The addition of ANF alone had similareffects to the addition of DA on the sodium pump, but when both were added together, the activity of Na+, K+-ATPase was decreased. Moreover, the extraneuronal uptake blocker, hydrocortisone, inhibited the latter effect. 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.