β-Adrenergic regulation of renin expression in differentiated U-937 monocytic cells

• Published in: Biochemical pharmacology Vol. 53; no. 12; pp. 1883 - 1888
• Main Authors: Jikihara, Hiroaki, Handwerger, Stuart, Poisner, Alan M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15-06-1997; Elsevier Science
• Subjects: 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology; angiotensin; Biological and medical sciences; Bucladesine - pharmacology; Cell Differentiation - drug effects; Cell Line; Cell physiology; Cell receptors; Cell structures and functions; Colforsin - pharmacology; cyclic AMP; cytokines (TNF-α, interferon-γ); Enzyme Precursors - biosynthesis; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; macrophage; Macrophages - metabolism; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Monocytes - drug effects; Monocytes - metabolism; Phorbol 12,13-Dibutyrate; phorbol ester; prorenin; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; renin; Renin - biosynthesis; Renin - genetics; Signal transduction; Terbutaline - antagonists & inhibitors; Terbutaline - pharmacology; U-937 cells; β-adrenergic; PDBU; phorbol ester; JGA; GADPH; macrophage; cytokines (TNF-α, interferon-γ); cAMP; RT—PCR; LPS; PDE; IFN-γ; U-937 cells; TNF-α; renin; FBS; angiotensin; ANGIO; cyclic AMP; prorenin; β-adrenergic; Agonist; Esterases; Activation; Phosphoric diester hydrolases; β-Adrenergic receptor; Terbutaline; Signal transduction; Messenger RNA; Renin; Established cell line; Prorenin; Lipopolysaccharide; Aspartic endopeptidases; 3',5'-Cyclic-nucleotide phosphodiesterase; Monocyte; Enzyme; Secretion; Cytokine; Cyclic AMP; Enzyme inhibitor; Peptidases; Angiotensin; Forskolin; Hydrolases; Macrophage
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(97)00058-0

Previous studies from our laboratories demonstrated that human decidual macrophages and peripheral mononuclear cells express renin. In the present study, we found that U-937 monocytes, induced to differentiate into macrophage-like cells by treatment with phorbol dibutyrate (PDBU), express renin mRNA and release renin (95% of which is in the form of prorenin). Treatment of these PDBU-exposed cells with dibutyryl-cAMP (1 mM) caused a 20-fold increase in renin mRNA and a 10-fold increase in prorenin release. Forskolin (10 μM), an activator of adenylyl cyclase, and terbutaline (100 μM), a
β
2-adrenergic agonist known to increase cAMP levels, also increased renin mRNA and prorenin release. The secretory response to terbutaline was potentiated by the type IV cyclic AMP-phosphodiesterase (PDE) inhibitor Ro 20–1724 (50 μM). Angiotensin II agonist inhibited the stimulatory effect of terbutaline on renin secretion as did the cytokines tumor necrosis factor-α and lipopolysaccharide plus interferon-γ. Since other studies have shown that U-937 cells possess
β
2-adrenergic receptors and express mainly the type IV PDE, the present findings strongly suggest that β-adrenergic receptors in mononuclear cells are coupled to renin expression via the cAMP transduction pathway. The results support a possible role for the renin-angiotensin system in macrophage function and suggest potential autocrine regulatory mechanisms in prorenin expression.