TRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain. TRPM3 mediates spontaneous Ca2+ entry and nonselective cation currents in transiently transfected human embryonic kidney 293 cells. Using measurements with the Ca2+-sensitive fluorescent dye fura-2 and the whole-cell patch-clamp technique, we found ...

Sphingosine-1-phosphate (SPP) was initially described as an intermediate in the metabolic pathway of long-chain sphingoid bases1). However, it is now widely accepted as a unique bioactive lipid messenger. It acts as a second messenger to regulate proliferation and survival intracellularly, and as a ligand for G protein-coupled receptors of the EDG-1 subfamily extracellularly2-4). SPP is involve...

The first enantioselective synthesis of chiral isosteric phosphonate analogues of FTY720 is described. One of these analogues, FTY720-(E)-vinylphosphonate (S)-5, but not its R enantiomer, elicited a potent antiapoptotic effect in intestinal epithelial cells, suggesting that it exerts its action via the enantioselective activation of a receptor. (S)-5 failed to activate the sphingosine 1-phospha...

BACKGROUND AND PURPOSE FTY720 is a known sphingosine 1-phosphate receptor agonist. In the present study, we investigated the neuroprotective effect of postischemic administration of FTY720 in rats with 2 hours transient middle cerebral artery occlusion (MCAO). METHODS One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of ...

The physiological significance of sphingosine 1-phosphate (S1P) transport in blood has been debated. We have recently reported a comprehensive sphingolipid profile in human plasma and lipoprotein particles (VLDL, LDL, and HDL) using HPLC-MS/MS (Hammad et al., 2010). We now determined the relative concentrations of sphingolipids including S1P in the plasma subfraction containing lipoproteins com...

sphingosine from ceramides by ceramidase, and the production of sphingosine-l-phosphate from sphingosine by sphingosine kinase. The most abundant types of SM and Cer have structures 1 and 2, respectively, in which the amino nitrogen beqrs a palmitoyl grQup. It has redently b6en demoristrated bY Takahata') that, by incubating PC 12 cells with docosahexaenoic acid (DHA)-abundant fish oil, the pal...

BACKGROUND AND PURPOSE Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study i...

Platelets are known to store a large amount of the bioactive lipid molecule sphingosine 1-phosphate (S1P) and to release it into the plasma in a stimuli-dependent manner. Erythrocytes can also release S1P, independently from any stimuli. We measured the S1P and sphingosine (Sph) levels in erythrocytes by HPLC and found that the contribution of erythrocyte S1P to whole blood S1P levels is actual...