Dexamethasone upregulates atrial natriuretic peptide c-receptor
protein in human mesangial cells without affecting mrna.
Ardaillou, Nicole, V[acute]eronique Blaise, Sandrine Placier,
Fran[cedilla]coise Amestoy, and Raymond Ardaillou.
INSERM 64, H[circumflex]opital Tenon, Paris, France
APStracts 2:0162F, 1995.
The objective of this study was to examine the role of dexamethasone
on the expression of B- and C-natriuretic peptide receptors (ANPR-B,
ANPR-C) in cultured human mesangial cells which only possess these
two subtypes. Dexamethasone caused concentration- and time-dependent
increases in 125 I-ANP binding which were prevented by glucocorticoid
receptor inhibition with RU ? 38486. A lag time of 24 ? hours and a
concentration of dexamethasone of at least 1 ? nmol/l were necessary
for this effect to occur. Dexamethasone-induced upregulation of 125
I-ANP binding resulted from increased receptor density. No change in
K D was observed. Only ANPR-C were affected by dexamethasone. Indeed,
dexamethasone did not modify C-type natriuretic peptide (CNP)
-dependent cGMP production by mesangial cells. Moreover, dexamethasone
upregulated ANPR-C protein expression as shown by Western blot
analysis and 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
post-transcriptional stage. Thus dexamethasone may influence
natriuretic peptide availability at their glomerular target sites.
Received 10 April 1995; accepted in final form 11 September 1995.
APS Manuscript Number F119-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.