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

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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Angiotensin II
Electrolytes
Rabbits
Acids
Ketoconazole
Phospholipases A2
Extracellular Space
GTP-Binding Proteins
Adenylyl Cyclases
Cultured Cells
Epithelium
Salts

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Nephrology

Cite this

Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule. / Romero, Michael F; Hopfer, U.; Madhun, Z. T.; Zhou, W.; Douglas, J. G.

In: Renal Physiology and Biochemistry, Vol. 14, No. 4-5, 1991, p. 199-207.

Research output: Contribution to journalArticle

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