Sphingosine 1-phosphate (S1P) regulates vascular contraction via S1P3 receptor: investigation based on a new S1P3 receptor antagonist.

Sphingosine 1-phosphate (S1P) induces diverse biological responses in various tissues by activating specific G protein-coupled receptors (S1P(1)-S1P(5) receptors). The biological signaling regulated by S1P(3) receptor has not been fully elucidated because of the lack of an S1P(3) receptor-specific antagonist or agonist. We developed a novel S1P(3) receptor antagonist, 1-(4-chlorophenylhydrazono)-1-(4-chlorophenylamino)-3,3-dimethyl- 2-butanone (TY-52156), and show here that the S1P-induced decrease in coronary flow (CF) is mediated by the S1P(3) receptor.

Inhibitory effects of isoliquiritigenin and licorice extract on voltage-dependent K(+) currents in H9c2 cells.

The effect of isoliquiritigenin (ISL), a component of licorice, on the voltage-dependent, ultra-rapidly activating delayed-rectifier K(+) current (IKur) was examined in H9c2 cells, a cell-line derived from rat cardiac myoblasts. IKur was recorded using the whole-cell patch clamp method with a pipette solution containing 140 mM K(+). Depolarizing voltage pulses of 200-ms duration were given with 10-mV steps every 10 s from -40 mV holding potential.

Pharmacophore-based design of sphingosine 1-phosphate-3 receptor antagonists that include a 3,4-dialkoxybenzophenone scaffold.

Sphingosine 1-phosphate (S1P) receptors are G-protein-coupled receptors. Among the five identified subtypes S1P1-5, the S1P3 receptor expressed on vascular endothelial cells has been shown to play an important role in cell proliferation, migration, and inflammation. A pharmacophore-based database search was used to identify a potent scaffold for an S1P3 receptor antagonist by common feature-based alignment and further validated using the Güner-Henry (GH) scoring method.

Peptide mimics of epidermal growth factor (EGF) with antagonistic activity.

Epidermal growth factor is a potent growth-promoting factor for a variety of tissue cells in vivo and in vitro. Epidermal growth factor binds, phosphorylates, and activates epidermal growth factor receptors on the cell surface. In this study, we attempted to design functional peptide mimics by panning a phage display library on the anti-epidermal growth factor monoclonal antibody.