The increase in the intracellular Ca2+ concentration ([Ca2+](i)) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca2+](i) by inhibiting the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca2+ pump. The results showed that addition of sphingosine produced a release of Ca2+ from the endoplasmic reticulum followed by a Ca2+ entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca2+](i) in mammalian cells. (C) 2016 Elsevier Inc. All rights reserved.