Beta-adrenergic regulation of renin expression in differentiated U-937 monocytic cells.
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 microM), an activator of adenylyl cyclase, and terbutaline (100 microM), a beta2-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 microM). Angiotensin II agonist inhibited the stimulatory effect of terbutaline on renin secretion as did the cytokines tumor necrosis factor-alpha and lipopolysaccharide plus interferon-gamma. Since other studies have shown that U-937 cells possess beta2-adrenergic receptors and express mainly the type IV PDE, the present findings strongly suggest that beta-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.
Jikihara
H
H
Division of Endocrinology, Children's Hospital Medical Center and Perinatal Research Institute, University of Cincinnati College of Medicine, OH 45229, USA.
Handwerger
S
S
Poisner
A M
AM
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics; D013726:Terbutaline / Q000037:antagonists & inhibitors / Q000494:pharmacology
D004792:Enzyme Precursors; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D012083:Renin; D013726:Terbutaline