Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule

M. F. Romero, U. Hopfer, Z. T. Madhun, W. Zhou, J. G. Douglas

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Angiotensin II (AngII) is a potent regulator of electrolyte transport with biphasic effects on salt and HCO3-resorption in proximal tubule epithelia (PCT). In cultured PCT cells, pM to nM AngII activates a GTP-binding protein to inhibit cAMP formation and thus releases inhibition of apical Na/H exchange. Phospholipase A2 is activated by nM to μM AngII releasing arachidonate which is metabolized by a novel P450 epoxygenase to form 5,6-epoxy-eicosatrienoic acid (5,6-EET). 5,6-EET and nM apical AngII cause dihydropyridine-sensitive Ca2+ influx from the extracellular space, inhibition of apical-to-basolateral Na flux, and decrease in epithelial monolayer short circuit current. 5,6-EET also inhibits Na/K-ATPase by 50%. This P450 epoxygenase is physiologically important in the AngII-signaling system because the P450 inhibitor ketoconazole blocks AngII effects while potentiating exogenous 5,6-EET effects. Finally, these AngII-mediated signaling systems are polarized in the PCT with pM basolateral AngII inhibiting adenylate cyclase and nM apical AngII activating PLA2 and subsequent generation of 5,6-EET.

Original languageEnglish (US)
Pages (from-to)199-207
Number of pages9
JournalRenal Physiology and Biochemistry
Volume14
Issue number4-5
StatePublished - 1991

Keywords

  • 5,6-EET
  • Na transport
  • P450 epoxygenase
  • angiotensin II
  • arachidonic acid
  • cAMP
  • calcium
  • cell culture
  • epithelial electrolyte transport
  • metabolism
  • proximal tubule

ASJC Scopus subject areas

  • Physiology
  • Nephrology

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