The present study aimed at investigating the influence of imidazoline receptor ligands on the proliferation of PC12 cells and the involvement of the sphingosine-1-phosphate (S1P) signaling system in this effect. In cultured PC12 cells, S1P (0.3-100 nM) and the I(1) imidazoline receptor ligands moxonidine (0.3 and 1 mM), agmatine (1 mM), idazoxan (10-100 microM) and efaroxan (1-100 microM) conce...

Sphingosine 1-phosphate (S1P) initiates T and B cell exit from lymphoid tissues by activating the S1P(1) receptor on lymphocytes. To define the mechanistic details of this ligand-receptor interaction, the biological activity of the S1P-blocking Ab Sphingomab was investigated. Treatment of mice with Sphingomab resulted in blood B and T cell lymphopenia. Although Sphingomab blocked S1P(1)-mediate...

Sphingosine 1‑phosphate (S1P) belongs to a significant group of signaling sphingolipids and exerts most of its activity as a ligand of G‑protein‑coupled receptors. In our previous study, S1P demonstrated a novel biological activity with the anti‑adipogenesis of 3T3‑L1 preadipocytes. In the present study, we identified a possible mechanism of S1P‑mediated anti‑adipogenic effects, particularly in...

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro bloo...

There is an increasing body of evidence demonstrating a critical role for the bioactive lipid S1P (sphingosine 1-phosphate) in cancer. S1P is synthesized and metabolized by a number of enzymes, including sphingosine kinase, S1P lyase and S1P phosphatases. S1P binds to cell-surface G-protein-coupled receptors (S1P1-S1P5) to elicit cell responses and can also regulate, by direct binding, a number...

Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1-5) in order to influence a broad spectrum of biological processes. This...

There is a need to better understand the mechanism of airway hyper-reactivity, a key feature of asthma. Evidence suggests that sphingosine-1-phosphate (S1P) could be a major player in this phenomenon. The purpose of this work was to define the S1P receptor responsible for this phenomenon. We have studied, in the rat, the effect of two S1P synthetic receptor ligands, 2-amino-2-[2-(4-octylphenyl)...

Sphingosine-1-phosphate (S1P), a multifunctional phospholipid, regulates vascular cell function. Whether S1P influences vascular inflammatory responses, particularly in hypertension, is unclear. We tested the hypothesis that S1P is a proinflammatory mediator signaling through receptor tyrosine kinase transactivation and that responses are amplified in vascular smooth muscle cells from stroke-pr...

Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1...

Sphingosine-1-phosphate (S1P) has been demonstrated to enhance endothelial barrier function in vivo and in vitro. However, different S1P receptor subtypes have been indicated to play different or even opposing roles in the regulation of vascular barrier function. This study aims to differentiate the roles of endogenous endothelial S1P subtype receptors in the regulation of permeability in intac...