Sphingosine 1-phosphate (S1P) induces diverse biological responses in various tissues by activating specific G protein-coupled receptors (S1P1–S1P5 receptors) [2]. TY-52156 is a potent and selective S1P3 receptor antagonist with a Ki value of 110 nM. In functional studies, TY-52156 showed submicromolar potency and a high degree of selectivity for S1P3 receptor. Effect of TY-52156 on both the S1P-induced increase in intracellular calcium ([Ca2+]i) and Rho activation that are responsible for the contraction of human coronary artery smooth muscle cells had been investigated. TY-52156 inhibited both the S1P-induced increase in [Ca2+]i and Rho activation [2]. TY-52156 inhibited FTY-720-induced S1P3 receptor-mediated bradycardia in vivo. These results clearly show that TY-52156 is both sensitive and useful as an S1P3 receptor-specific antagonist and reveal that S1P induces vasoconstriction by directly activating S1P3 receptor and through a subsequent increase in [Ca2+]i and Rho activation in vascular smooth muscle cells [2].
搜索
