Sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is an agonist of S1P_1-5 receptors and a ligand of GPR3, GPR6 and GPR12. Sphingosine-1-phosphate is an intracellular second messenger and mobilizes Ca²⁺ as an extracellular ligand for G protein-coupled receptors^[1]. Sphingosine-1-phosphate is an important lipid mediator generated from Sphingomyelin (HY-113498) or other membrane phospholipids^[2]. Sphingosine-1-phosphate stimulates the DNA synthesis, cell proliferation and migration^[4]. In Vitro:S1P (1 μM) induces a significant Ca²⁺ releases in HEK293 cells under serum starvation conditions (1% FCS)^[1].
In a functional Ca²⁺ assay, Suramin (HY-B0879) alone does not exert any effect on intracellular Ca²⁺ release via gpr3, gpr6 or gpr12. In contrast, S1P (1 μM) induces Ca²⁺ release of gpr3, gpr6 and gpr12 in the presence of Suramin (HY-B0879) various concentrations in transfected HEK293 cells^[2].
In a functional Ca²⁺ assay,S1P (3-3000 nM) in the presence Suramin (300 μM), exhibits nanomolar EC₅₀ values for gpr3 (EC₅₀=29 nM), gpr6 (EC₅₀=15 nM) and gpr12 (EC₅₀=24 nM), rat gpr3 (EC₅₀=68 nM),respectively in HEK293 cells^[2].
S1P increases intracellular calcium levels in TAg-Jurkat cells expressing S1P1 and G_qi5, which allows for phospholipase C stimulation by G_i proteins, when used at a concentration of 200 nM, as well as in TAg-Jurkat cells expressing S1P2 and S1P3 receptors (EC₅₀s = 8 and 11 nM, respectively)^[3].