Potentiation of endothelin-1-induced prostaglandin E2 formation by Ni2+ and Sr2+ 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 E 2 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 A 2 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.