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Glucocorticoid Regulation of Atrial Natriuretic Peptide Receptors on Cultured Endothelial Cells^*

KATHERINE L. LANIER-SMITH and MARK G. CURRIE

Department of Cell and Molecular Pharmacology and Experimental Therapeutics (K.L.L.S.), Medical University of South Carolina Charleston, South Carolina 29425
Monsanto Company (M.G.C.) St. Louis, Missouri 63167

Address all correspondence and requests for reprints to: Dr. Mark G. Currie, Monsanto Company T3P, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167.

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 µM) produced a 69.3 ± 23% (P < 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 µg/ml), indicating a requirement for protein synthesis. The glucocorticoid receptor antagonist RU 486 completely inhibited the dexamethasone effect. In affinity cross-linking experiments, dexamethasone increased the labeling 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 < 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. (Endocrinology 129: 2311–2317,1991)

Footnotes

^* This work was supported by a grant from the American Heart Association.

Recipient of an American Heart Association-CIBA-Geigy Established Investigatorship Award.

Received April 22, 1991.

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