REGULATION BY SPHINGOMYELINASE AND SPHINGOSINE OF CA2-ANTIBODY, THAPSIGARGIN, OR IONOMYCIN IN THE JURKAT T-CELL LINE( SIGNALS ELICITED BY CD3 MONOCLONAL)

Sphingomyelinase induces a marked rapid decrease of cytosolic Ca2+ con centration in Jurkat T cells treated with either CD3 monoclonal antibo dy; the Ca2+-ATPase inhibitor, thapsigargin; or the Ca2+ ionophore, io nomycin. Sphingomyelinase treatment of Jurkat cells results in a net d ecrease of cellular sphingomyelin content. Among the products generate d by the catabolism of sphingomyelin, sphingosine displayed exactly th e same effect as sphingomyelinase. Sphingosine decreases the cytosolic Ca2+ concentration in cells treated with CD3, thapsigargin, or ionomy cin. Studying the effect of sphingosine in CD3-activated cells showed that this compound does not modify Ca2+ mobilization from intracellula r stores but strongly inhibited the Ca2+ influx induced by the monoclo nal antibody. The fact that sphingosine inhibits Ca2+ influx generated by thapsigargin and ionomycin supports the hypothesis that the drug a ctivates the Ca2+ extrusion process. Derivatives of sphingosine such a s erythrosphinganine and threosphinganine share the same inhibitory pr operties,