Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells

Cell Signal. 1990;2(1):67-76. doi: 10.1016/0898-6568(90)90034-8.


The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.

Publication types

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

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / pharmacology
  • Angiotensinogen / biosynthesis*
  • Carcinoma, Hepatocellular / pathology
  • Colforsin / pharmacology
  • Cyclic AMP / physiology
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / physiology*
  • Glucagon / pharmacology
  • Humans
  • Liver Neoplasms / pathology
  • Neoplasm Proteins / biosynthesis
  • Pertussis Toxin*
  • Protein Processing, Post-Translational
  • Second Messenger Systems / drug effects*
  • Tumor Cells, Cultured / drug effects
  • Virulence Factors, Bordetella / pharmacology*


  • Neoplasm Proteins
  • Virulence Factors, Bordetella
  • Angiotensinogen
  • Angiotensin II
  • Colforsin
  • Adenosine Diphosphate Ribose
  • angiotensin II, Sar(1)-Val(5)-
  • Glucagon
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins