We have examined the Ca2+ release activity of sphingolipid-derivatives from rat brain microsomes using a Fura-2 cytofluorometric assay. Sphingosylphosphorylcholine, lysosphingomyelin, elicited a rapid Ca2+ release from both cerebral and cerebellar microsomes. Other compounds including sphingosine and sphingosine-1-phosphate were incapable of causing the Ca2+ release. The pharmacological properties suggest that the sphingosylphosphorylcholine-elicited Ca2+ mobilization is not mediated by inositol 1,4,5-triphosphate receptors. Immunocytochemical study showed the occurrence of sphingomyelin, a putative precursor for sphingosylphosphorylcholine, in the somatodendritic membrane domains of cerebellar neurons. These observations imply that sphingosylphosphorylcholine is a potent Ca2+ releaser in brain neurons.
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