Angiotensin-(1-7) can interact with the rat proximal tubule AT4 receptor system

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35 Scopus citations

Abstract

This study was undertaken to identify the non-AT1, non-AT2 angiotensin receptor that mediates the ANG-(1-7) inhibitory action on rat proximal tubule transport processes. ANG-(1-7) inhibited nystatin-stimulated, ouabain- suppressible O2 consumption (QO2) rates in freshly isolated rat proximal tubules (reflecting reduced basolateral Na+-K+-ATPase activity). Selective angiotensin-receptor subtype antagonists revealed that AT1 and AT4 receptors mediated the response of ANG-(1-7). Receptor autoradiography of the rat kidney demonstrated a high density of AT1 and AT4 receptors and no specific 125I-ANG-(1-7) binding sites. Competition assays in rat kidney sections indicated that ANG-(1-7) competed predominantly for the AT1 receptor site, whereas its NH2-terminal-deleted metabolite, ANG-(3-7), competed primarily for the AT4-receptor site. Metabolism of 125I-ANG-(1- 7) in rat proximal tubules generated peptide fragments that included ANG-(3- 7), with the pentapeptide producing a concentration-dependent inhibition of nystatin-stimulated proximal tubule QO2 that was abolished by AT4-receptor blockade. These results suggest that the generation of ANG-(3-7) from the NH2-terminal metabolism of ANG-(1-7) caused the interaction of the parent peptide with the proximal tubule AT4 receptor, which elicited a decrease in energy-dependent solute transport.

Original languageEnglish (US)
Pages (from-to)F75-F83
JournalAmerican Journal of Physiology - Renal Physiology
Volume277
Issue number1 46-1
StatePublished - Jul 1 1999
Externally publishedYes

Keywords

  • Angiotensin IV
  • Angiotensin receptor subtypes
  • Angiotensin-(3-7)
  • Metabolism
  • Transport

ASJC Scopus subject areas

  • Physiology
  • Urology

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