Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions

The concentration of sphingosine 1-phosphate (S1P) in plasma or serum is mu ch higher than the half-maximal concentration of the sphingolipid needed to stimulate its receptors. Nevertheless, the inositol phosphate response to plasma or serum mediated by Edg-.3, one of the S1P receptors, which was ove rexpressed in Chinese hamster ovary cells, was much smaller than the respon se expected from the total amount of S1P in these samples. The inositol pho sphate response to exogenous S1P was markedly attenuated in the presence of charcoal-treated low-S1P serum. The inhibitory effect was lost by boiling but not by dialysis of the serum. The inhibitory action of the serum was sp ecific to S1P and was associated with the trapping of exogenous S1P; the in ositol phosphate response to P-2-purinergic agonists was somewhat enhanced by the charcoal-treated serum. Among the components of plasma or serum, lip oproteins such as low-density and high-density lipoproteins showed a strong er activity for trapping S1P than lipoprotein-deficient serum. Consistent w ith this observation, we detected a 15-100-fold higher amount of S1P per un it amount of protein in lipoproteins than in the lipoprotein-deficient seru m. Thus even though the protein content of the lipoprotein fraction contrib utes to only 4% of the total protein content of plasma or serum, more than 60% of S1P is distributed in this fraction. These results suggest that the tight binding of S1P to the components of serum or plasma, including lipopr oteins, may interfere with the S1P binding to its receptors and thereby att enuate the lipid-receptor-mediated actions in the cells.