Renal proximal tubular AT2 receptor: signaling and transport

J Am Soc Nephrol. 1999 Jan:10 Suppl 11:S69-74.


Previous studies have documented that the vasoactive agonist angiotensin II (AngII) directly affects proximal tubular sodium-bicarbonate reabsorption in a biphasic manner, whereby picomolar concentrations promote reabsorption and nanomolar concentrations have the converse effect. Although it is generally agreed that the AT1 receptor subtype mediates AngII-induced sodium-bicarbonate reabsorption primarily through adenylate cyclase, the receptor subtype mediating natriuresis is less well defined. Using mouse proximal tubular cells, this study documents AT1-dependent enhancement (candesartan-inhibitable) of bicarbonate reabsorption and AT2-induced (PD123319- and CGP42112A-inhibitable) decrement of bicarbonate absorption. The signaling mechanisms were examined in rabbit proximal tubule cells in culture. The AT2 signaling involves G protein beta- and gamma-mediated phospholipase A2 activation, arachidonic acid release, and downstream events linked to Shc/Grb2/Sos and p21ras rather than protein kinase C as reported previously for AngII receptors. These observations provide a novel mechanism for AngII-AT2 receptor-mediated transport modulation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin Receptor Antagonists
  • Animals
  • Arachidonic Acid / metabolism
  • Biological Transport / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / metabolism
  • Imidazoles / pharmacology
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Oligopeptides / pharmacology
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Pyridines / pharmacology
  • Rabbits
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin / metabolism*
  • Signal Transduction
  • Sodium Bicarbonate / metabolism


  • Angiotensin Receptor Antagonists
  • Imidazoles
  • Oligopeptides
  • Pyridines
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin
  • Angiotensin II
  • CGP 42112A
  • PD 123319
  • Arachidonic Acid
  • Sodium Bicarbonate
  • Phospholipases A
  • Phospholipases A2
  • GTP-Binding Proteins