Characterization and regulation of the angiotensin II type-1 receptor (binding and mRNA) in human adrenal fasciculata-reticularis cells.
The classical concept of human adrenal physiology indicates that only glomerulosa cells are the target of A-II. Herein, we demonstrated that cultured human adrenal fasciculata-reticularis cells were also responsive to this hormone. Indeed, these cells contained high affinity (Kd = 0.9-1.1 nM) and low capacity (8,000-13,000 sites/cell) A-II receptors, and more than 95% of them were of the type-1. These AT1 receptors are functional since A-II was able to increase cortisol production after 48 h of treatment. These effects were inhibited by losartan, an AT1 antagonist, but not by CGP42112A, an AT2 antagonist. The expression of the type-1 A-II receptor mRNA was detected in the whole adrenal in both adult and fetus, and in cultured human adrenal fasciculata-reticularis cells. In these cells A-II negatively regulated AT1 receptor mRNA, and this effect was also mediated through the AT1 receptor subtype.
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INSERM U307, Hôpital Debrousse, Lyon, France.
Lebrethon
M C
MC
Kermabon
A Y
AY
Rouer
E
E
Benarous
R
R
Saez
J M
JM
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D019808:Losartan; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014162:Transfection; D015383:Zona Fasciculata / Q000378:metabolism*; D015385:Zona Reticularis / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D019808:Losartan