Ang-(3-4) suppresses inhibition of renal plasma membrane calcium pump by Ang II.
We previously demonstrated that Ang II inhibits the renal plasma membrane Ca(2+)-ATPase. In the present work we have studied the effect of Ang II, at concentrations similar to those found in the renal interstitium, on the Ca(2+)-ATPase from proximal tubule cells. High Ang II concentration (5 x 10(-7) mol/L) led to the recovery of Ca(2+)-ATPase activity previously inhibited by 50% at low Ang II concentration (10(-10) mol/L). Reactivation occurred in parallel with: (i) formation of only two dead-end metabolites [Ang-(3-4) and Tyr] after incubation of isolated membranes with micromolar Ang II; and (ii) dissociation of constitutive AT(1)R/AT(2)R heterodimers, which are preserved with 10(-10) mol/L Ang II. When the membranes were incubated with 10(-14) mol/L Ang-(3-4), inhibition by 10(-10) mol/L Ang II was no longer observed. The counteracting effect of Ang-(3-4) was abolished by PD123319, an antagonist of AT(2)R, and mimicked by CGP42112A, an agonist of AT(2)R. Ang-(1-7) is an intermediate in the formation of Ang-(3-4) via a pathway involving angiotensin-converting enzyme (ACE), and complete dipeptide breakdown to Tyr and Val is impaired by low Ang II. We conclude that Ang-(3-4) may be a physiological regulator of active Ca(2+) fluxes in renal proximal cells by acting within the renin-angiotensin axis.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Flavia
F
Axelband
Iranaia
I
Assunção-Miranda
Isabela R
IR
de Paula
Fernanda M
FM
Ferrão
Juliana
J
Dias
Antonio
A
Miranda
Filipe
F
Miranda
Lucienne S
LS
Lara
Adalberto
A
Vieyra
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000819:agonists / Q000378:metabolism; D012756:Sheep; D021241:Spectrometry, Mass, Electrospray Ionization; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D009842:Oligopeptides; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D000252:Calcium-Transporting ATPases