DEXAMETHASONE UP-REGULATES ANP C-RECEPTOR PROTEIN IN HUMAN MESANGIAL CELLS WITHOUT AFFECTING MESSENGER-RNA

The objective of this study was to examine the role of dexamethasone o n the expression of natriuretic peptide B-type and C-type receptors (A NPR-B and ANPR-C) in cultured human mesangial cells, which only posses s these two subtypes. Dexamethasone caused concentration- and time-dep endent increases in I-125-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 necessa ry for this effect to occur. Dexamethasone-induced upregulation of I-1 25-ANP binding resulted from increased receptor density. No change in dissociation constant (K-d) was observed. Only ANPR-C were affected by dexamethasone. Indeed, dexamethasone did not modify C-type natriureti c peptide (i.e., CNP)-dependent cGMP production by mesangial cells. Mo reover, dexamethasone upregulated ANPR-C protein expression as shown b y 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 densit y on mesangial cells through a mechanism implying, successively, inter action with the glucocorticoid receptor and increase of ANPR-C protein synthesis at a posttranscriptional stage. Thus dexamethasone may infl uence availability of natriuretic peptides at their glomerular target sites.