Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells.
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.
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Department of Pharmacology, St. Louis University School of Medicine, Missouri.
Corvol
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Howlett
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D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000808:Angiotensinogen / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D037342:Pertussis Toxin; D011499:Protein Processing, Post-Translational; D015290:Second Messenger Systems / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D009363:Neoplasm Proteins; D010566:Virulence Factors, Bordetella; D000808:Angiotensinogen; D000804:Angiotensin II; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; C041007:angiotensin II, Sar(1)-Val(5)-; D005934:Glucagon; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins