title: Potentiation of endothelin-1-induced prostaglandin E2 formation by Ni(2+) and Sr(2+) in murine osteoblastic MC3T3-E1 cells.
abstract: Cation recognition mechanisms beyond calcium-sensing receptors are still largely unexplored and consequently there is surprisingly little information on linking of this primary event to key metabolic features of different cell systems, such as arachidonic acid metabolism. However, information on the modulatory role of extracellular cations in cellular function is scarce. In this study we have demonstrated, that Ni(2+) and Sr(2+) potentiate endothelin-1 induced prostaglandin E2 formation in the osteoblastic cell line, MC3T3-E1, even in the absence of extracellular calcium. The effect is strictly dependent of receptor-mediated signal transduction processes evoked by endothelin-1 and arachidonate release involves cytosolic phospholipase A2 activity. The ligation sites, at least for Ni(2+) are extracellular. The data suggest a novel activation mechanism for arachidonate release and subsequent prostaglandin formation that does not require calcium.
authors.affiliation: University Hospital of Youth and Adolescence Medicine, Medical University of Graz, Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Auenbruggerplatz 34/2, A-8036 Graz, Austria. Electronic address: hans.leis@medunigraz.at.
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Leis
authors.affiliation: University Hospital of Youth and Adolescence Medicine, Medical University of Graz, Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Auenbruggerplatz 34/2, A-8036 Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Windischhofer
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002412:Cations; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D019332:Endothelin-1 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D009532:Nickel / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D013324:Strontium / Q000494:pharmacology*
chemical_list: D002412:Cations; D019332:Endothelin-1; D007476:Ionophores; D000001:Calcimycin; D009532:Nickel; D051545:Cyclooxygenase 1; D054513:Group IV Phospholipases A2; D019204:GTP-Binding Proteins; D015232:Dinoprostone; D013324:Strontium
keywords: Endothelin; MC3T3-E1; Nickel; Osteoblast; Prostaglandin; Strontium