title: Urodilatin increases renal dopamine uptake: intracellular network involved.
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-1-one (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 signaling pathway, since urodilatin effects were mimicked by the analog 125 μM 8-Br-cGMP and blocked by the proteinkinase G-specific inhibitor, KT-5823 (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.
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC, CONICET, Junín 956, C 1113AAD, Buenos Aires, Argentina. marcelinkchoi@yahoo.com.ar
authors.forename: Marcelo R
authors.initials: MR
authors.lastname: Choi
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Citarella
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Lee
authors.forename: Florencia
authors.initials: F
authors.lastname: Lucano
authors.forename: Belisario E
authors.initials: BE
authors.lastname: Fernández
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine