Glucocorticoids regulate the expression of angiotensin AT1 receptors, in the human hepatoma cell line, PLC-PRF-5.
The effects of different steroids on the expression of angiotensin AT1 receptors by the human hepatoma cell line, PLC-PRF-5 was studied. Dexamethasone and aldosterone decreased the specific binding of [3H]angiotensin II to intact PLC-PRF-5 cells by 57 +/- 4% and 54 +/- 2%, respectively, compared to control, untreated cells. EC50 values for dexamethasone, cortisol and aldosterone were 1.8 +/- 0.6, 40 +/- 6, and 310 +/- 20 nM, respectively, suggesting that these effects were mediated via a glucocorticoid receptor. Scatchard analysis revealed that dexamethasone decreased the number of angiotensin AT1 receptors expressed (50 +/- 4% relative to control) with no change in receptor affinity. Treating cells with dexamethasone in the presence of either an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist did not prevent the reduction in angiotensin AT1 receptor expression, ruling out a mechanism involving a dexamethasone induced increase in endogenous angiotensin II production. A ribonuclease protection assay established that the steady state level of angiotensin AT1 receptor mRNA in dexamethasone treated cells was reduced to 34.7 +/- 8.4% of untreated cells. The decrease in the number of angiotensin AT1 receptors expressed on the cell surface after treatment with dexamethasone therefore seems likely to reflect the decreased steady state level of the mRNA coding for this receptor.
Wintersgill
H P
HP
Department of Cardiovascular Studies, University of Leeds, UK.
Warburton
P
P
Bryson
S E
SE
Ball
S G
SG
Balmforth
A J
AJ
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D057911:Angiotensin Receptor Antagonists; D005938:Glucocorticoids; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003907:Dexamethasone