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Am J Physiol Renal Physiol 270: F440-F446, 1996;
0363-6127/96 $5.00
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AJP - Renal Physiology, Vol 270, Issue 3 440-F446, Copyright © 1996 by American Physiological Society

ARTICLES

Dexamethasone upregulates ANP C-receptor protein in human mesangial cells without affecting mRNA

N. Ardaillou, V. Blaise, S. Placier, F. Amestoy and R. Ardaillou
Institut National de la Sante et de la Recherche Medicale 64, Hopital Tenon, Paris, France.

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.


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S. Placier, X. Bretot, N. Ardaillou, J.-C. Dussaule, and R. Ardaillou
Regulation of ANP clearance receptors by EGF in mesangial cells from NOD mice
Am J Physiol Renal Physiol, August 1, 2001; 281(2): F244 - F254.
[Abstract] [Full Text] [PDF]


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