Angiotensin II regulation of renal dopamine uptake and Na(+),K(+)-ATPase activity.
OBJECTIVE
Angiotensin II (ANG II) decreases dopamine (DA) uptake in renal cortex activating AT(1) receptors. We investigated the signaling pathways that mediate this action and the incidence of DA-ANG II interaction on renal Na(+),K(+)-ATPase activity.


METHODS
ANG II effects on [(3)H]-DA uptake and Na(+),K(+)-ATPase were measured in samples from the outer renal cortex of Sprague-Dawley rats.


RESULTS
Inhibition of the phospholipase C (PLC) pathway blunted ANG II inhibitory effects on [(3)H]-DA uptake, since U-73122, 2-APB, TMB-8, chelerythrine and KN-93 (PLC, IP(3)-dependent Ca(2+) release channels, IP(3) receptors, protein kinase C and CaM kinase II inhibitors, respectively) each one blocked ANG II effects. Inhibition of adenylate cyclase pathway did not modify ANG II inhibitory effects on DA uptake. ANG II effects on [(3)H]-DA uptake were able to modify Na(+),K(+)-ATPase activity in carbidopa-treated rats. Exogenous DA decreased while ANG II increased the enzyme activity. Neither the addition of DA together with ANG II, nor the extraneuronal DA uptake blocker hydrocortisone altered ANG II stimulatory effects on Na(+),K(+)-ATPase activity, but hydrocortisone blocked the inhibitory effects of exogenous DA.


CONCLUSIONS
Stimulation of renal AT(1) receptors by ANG II signals through the PLC pathway to inhibit extraneuronal DA uptake. DA and ANG II act through a common pathway involving reversible renal tubular Na(+),K(+)-ATPase deactivation and activation, respectively. In addition, ANG II by itself is able to stimulate renal Na(+),K(+)-ATPase activity.
Choi
Marcelo R
MR
Department of Pathophysiology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC, CONICET, Buenos Aires, Argentina.
Medici
Cecilia
C
Gironacci
Mariela M
MM
Correa
Alicia H
AH
Fernández
Belisario E
BE
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine