Urodilatin increases renal dopamine uptake: intracellular network involved
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ORIGINAL PAPER
Urodilatin increases renal dopamine uptake: intracellular network involved Marcelo R. Choi & Marisa R. Citarella & Brenda M. Lee & Florencia Lucano & Belisario E. Fernández
Received: 9 August 2010 / Accepted: 14 December 2010 / Published online: 6 January 2011 # University of Navarra 2011
Abstract Dopamine and urodilatin promote natriuresis and diuresis through a common pathway that involves reversible deactivation of renal Na+, K+ATPase. We have reported that urodilatin enhances dopamine uptake in outer renal cortex through the natriuretic peptide type A receptor. Moreover, urodilatin enhances dopamine-induced inhibition of Na+, K+-ATPase activity. The objective of the present work was to investigate the intracellular signals involved in urodilatin effects on dopamine uptake in renal cortex of kidney rats. We show that urodilatin-elicited increase in 3H-dopamine was blunted by methylene blue (10 μM), a non-specific guanylate cyclase inhibitor, and by phorbol-12-myristate-13-acetate (1 μM), a particulate guanylate cyclase inhibitor, but not by 1H-[1,2,4]-Oxadiazolo-[4,3-a]-quinoxalin-1one (10 μM), a specific soluble guanylate cyclase inhibitor; therefore the involvement of particulate guanylate cyclase on urodilatin mediated dopamine uptake was confirmed. Cyclic guanosine monophosphate and proteinkinase G were also implicated in the Marcelo R. Choi and Marisa R. Citarella contributed equally to this study. M. R. Choi (*) : M. R. Citarella : B. M. Lee : F. Lucano : B. E. Fernández Department of Pathophysiology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC, CONICET, Junín 956, C 1113 AAD, Buenos Aires, Argentina e-mail: [email protected]
signaling pathway, since urodilatin effects were mimicked by the analog 125 μM 8-Br-cGMP and blocked by the proteinkinase G-specific inhibitor, KT5823 (1 μM). In conclusion, urodilatin increases dopamine uptake in renal cortex stimulating natriuretic peptide type A receptor, which signals through particulate guanylate cyclase activation, cyclic guanosine monophosphate generation, and proteinkinase G activation. Dopamine and urodilatin may achieve their effects through a common pathway that involves deactivation of renal Na+, K+-ATPase, reinforcing their natriuretic and diuretic properties. Keywords Urodilatin . Dopamine . Guanylate cyclase . PKG . Kidney
Introduction Urodilatin is a 32-amino acid peptide, discovered in 1988 from human urine, identical to the circulating form of atrial natriuretic peptide (ANP), except for four extended amino acids at the N terminus [15]. Dopamine, endogenously produced by renal proximal tubules, plays an important autocrine/paracrine role in the regulation of renal function [12]. Dopamine effects on renal sodium handling consist of a large increase in urinary sodium excretion, which is dependent on Na+, K+-ATPase activity inhibition, and of diverse sodium influx pathways, in both proximal and distal tubular cells [7]. These effects are mainly
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mediated via the dopamine-1 receptor subtype,
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