Angiotensin II stimulates angiotensinogen synthesis in hepatocytes by a pertussis toxin-sensitive mechanism.
The role of intracellular messengers in the stimulatory effect of angiotensin II on angiotensinogen synthesis and secretion in hepatocytes was examined. Angiotensinogen secretion was not influenced by modulators of intracellular calcium (calmidazolium, A 23187, Bay K 8644, methoxamine). In contrast, agents decreasing intracellular cAMP (angiotensin II, guanfacine) stimulated, and those increasing cAMP (isoproterenol, glucagon, forskolin) depressed angiotensinogen secretion. An inverse relationship was also observed between cAMP and angiotensinogen mRNA. Pretreatment of hepatocytes with pertussis toxin abolished the stimulation by angiotensin II. It is concluded that angiotensin II-induced stimulation of angiotensinogen synthesis is initiated by inhibition of adenylate cyclase.
Klett
C
C
Department of Pharmacology, University of Heidelberg, FRG.
Muller
F
F
Gierschik
P
P
Hackenthal
E
E
D037361:Adenylate Cyclase Toxin; D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D014316:Tritium; D000808:Angiotensinogen; D000804:Angiotensin II; D005934:Glucagon; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007930:Leucine