N-acetyl-sphingenine-1-phosphate is a potent calcium mobilizing agent

Calcium mobilization induced by phosphorylated sphingoid bases was analyzed in calf pulmonary artery endothelial cells by confocal microscopy. A sphingenine-1-phosphate (SeP) analogue, N-acetyl-sphingenine-1-phosphate (N-C-2-SeP), exogenously added to these cells, caused a fast and transient intracellular rise in calcium and was as potent as SeP, A minimal concentration of 0.6 nM for N-C-2-SeP versus 1 nM for SeP was determined, The N-C-2-SeP-induced Ca2+-signaling, like the response to SeP, was due to a release from thapsigargin-sensitive, ryanodine-insensitive, intracellular Ca2+- stores and not to a Ca2+-influx, N-C-2-SeP can be considered as a truncated ceramide-phosphate, a lipid already reported to be mitogenic (Gomez-Munoz, A., Duffy, P.A., Martin, A., O'Brien, L., Byun, H.S., Bittman, R, and Brindley, D.N. (1995) Mol. Pharmacol, 47, 833-839), an effect that might be secondary to Ca2+-mobilization. (C) 1999 Federation of European Biochemical Societies.