Ang-(3-4) suppresses inhibition of renal plasma membrane calcium pump by Ang II

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2009-06-05
Autores
Axelband, Flavia
Assuncao-Miranda, Iranaia
Paula, Isabela R. de
Ferrao, Fernanda M.
Dias, Juliana
Miranda, Antonio [UNIFESP]
Miranda, Filipe
Lara, Lucienne S.
Vieyra, Adalberto
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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). Reacdvation 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/LAng II. When the membranes were incubated with 10(-14) mol/LAng-(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. (C) 2009 Elsevier B.V. All rights reserved.
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Regulatory Peptides. Amsterdam: Elsevier B.V., v. 155, n. 1-3, p. 81-90, 2009.
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