title: Catecholamines in a macrophage cell line.
abstract: This study provides the first evidence for catecholamine synthesis and release in the RAW264.7 cell line, an important macrophage model. Although catecholamines were low in unstimulated cells, activation with lipopolysaccharide (LPS) induced tyrosine hydroxylase (TH) mRNA and increased extracellular norepinephrine and intracellular dopamine within 48 h. The catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (alpha-mpt) decreased extracellular norepinephrine levels, suggesting release and rapid turnover of newly synthesized norepinephrine. High concentrations of dopamine or norepinephrine (>/=100 microM) decreased proliferation and increased apoptosis of macrophages. These anti-proliferative effects were prevented by simultaneous treatment with the anti-oxidant ascorbic acid. Pre-incubation with a glutathione synthesis inhibitor (L-buthionine-[S,R]-sulfoximine [L-BSO]) increased sensitivity to catecholamine-stimulated apoptosis, suggesting that glutathione protects macrophages from both endogenous and exogenous catecholamines.
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Brown
authors.forename: Randall T
authors.initials: RT
authors.lastname: Meyers
authors.forename: Karen M
authors.initials: KM
authors.lastname: Brennan
authors.forename: Julie M
authors.initials: JM
authors.lastname: Rumble
authors.forename: Nedathur
authors.initials: N
authors.lastname: Narasimhachari
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Perozzi
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Stewart
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer-Stenger
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase