Glucocorticoid regulation of atrial natriuretic peptide receptors on cultured endothelial cells.

Abstract:

:Cultured pulmonary artery endothelial (CPAE) cells possess specific high affinity receptors for atrial natriuretic peptide (ANP). CPAE cells were used to investigate the regulation of ANP receptors by glucocorticoids. Treatment of CPAE cells with dexamethasone (1 microM) produced a 69.3 +/- 23% (P less than 0.01) increase in the maximum binding of [125I]ANP to CPAE cells without affecting the affinity of binding. The EC50 for the dexamethasone effect was approximately or equal to 0.5 nM, with a maximum effect at 10 nM. The effect was time dependent and developed over 16-72 h, and it could be inhibited by cycloheximide (0.075 micrograms/ml), indicating a requirement for de novo protein synthesis. The glucocorticoid receptor antagonist RU 486 completely inhibited the dexamethasone effect. In affinity cross-linking experiments, dexamethasone increased the labelling of the ANP-R2, or clearance, receptor, whereas labeling of the ANP-R1 receptor could not be detected. Despite the increase in maximum binding, dexamethasone treatment produced a significant (P less than 0.01) decrease in the ANP-stimulated cyclic GMP response of CPAE cells and no change in the affinity of binding for the truncated ANP analog, atriopeptin I. These results indicate that the dexamethasone effect is mediated through glucocorticoid receptors and may be selective for the nonguanylate cyclase-coupled, or ANP-R2, receptor subtype. This study provides direct evidence for regulation of ANP receptors by steroid hormones.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Lanier-Smith KL,Currie MG

doi

10.1210/endo-129-5-2311

subject

Has Abstract

pub_date

1991-11-01 00:00:00

pages

2311-7

issue

5

eissn

0013-7227

issn

1945-7170

journal_volume

129

pub_type

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