Dexamethasone upregulates ANP C-receptor protein in human mesangial cells without affecting mRNA.
The objective of this study was to examine the role of dexamethasone on the expression of natriuretic peptide B-type and C-type receptors (ANPR-B and ANPR-C) in cultured human mesangial cells, which only possess these two subtypes. Dexamethasone caused concentration- and time-dependent increases in 125I-labeled ANP binding, which were prevented by glucocorticoid receptor inhibition with RU-38486. A lag time of 24 h and a concentration of dexamethasone of at least 1 nmol/l were necessary for this effect to occur. Dexamethasone-induced upregulation of 125I-ANP binding resulted from increased receptor density. No change in dissociation constant (Kd) was observed. Only ANPR-C were affected by dexamethasone. Indeed, dexamethasone did not modify C-type natriuretic peptide (i.e., CNP)-dependent cGMP production by mesangial cells. Moreover, dexamethasone upregulated ANPR-C protein expression as shown by Western blot analysis and by an increase in ANPR-C immunoreactivity at the cell surface. In contrast, dexamethasone did not modify ANPR-C mRNA expression. In conclusion, glucocorticoids increase ANPR-C density on mesangial cells through a mechanism implying, successively, interaction with the glucocorticoid receptor and increase of ANPR-C protein synthesis at a posttranscriptional stage. Thus dexamethasone may influence availability of natriuretic peptides at their glomerular target sites.
Ardaillou
N
N
Institut National de la Santé et de la Recherche Médicale 64, Hôpital Tenon, Paris, France.
Blaise
V
V
Placier
S
S
Amestoy
F
F
Ardaillou
R
R
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis*; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C