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Last update 23 Jan 2025

Lysosphingolipid receptor

Last update 23 Jan 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with Lysosphingolipid receptor

VPC-51299

Target

Lysosphingolipid receptor

Mechanism

Lysosphingolipid receptor agonists

Active Org.-

Originator Org.

Catena Pharmaceuticals, Inc.

Active Indication-

Inactive Indication

Fibrosis [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Lysosphingolipid receptor

100 Translational Medicine associated with Lysosphingolipid receptor

0 Patents (Medical) associated with Lysosphingolipid receptor

Literatures (Medical) associated with Lysosphingolipid receptor

01 Jul 2019·Journal of Experimental MedicineQ1 · MEDICINE

Lysolipid receptor cross-talk regulates lymphatic endothelial junctions in lymph nodes

Q1 · MEDICINE

Article

Author: Engelbrecht, Eric ; Aoki, Junken ; Xiong, Yanbao ; Cartier, Andreane ; Ishida, Satoru ; Bromberg, Jonathan S. ; Proia, Richard L. ; Ono, Yuki ; Galvani, Sylvain ; Hisano, Yu ; Kawakami, Kouki ; Inoue, Asuka ; Kano, Kuniyuki ; Kono, Mari ; Yanagida, Keisuke ; Kuo, Andrew ; Hla, Timothy ; Piao, Wenji

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) activate G protein–coupled receptors (GPCRs) to regulate biological processes. Using a genome-wide CRISPR/dCas9–based GPCR signaling screen, LPAR1 was identified as an inducer of S1PR1/β-arrestin coupling while suppressing Gαi signaling. S1pr1 and Lpar1-positive lymphatic endothelial cells (LECs) of lymph nodes exhibit constitutive S1PR1/β-arrestin signaling, which was suppressed by LPAR1 antagonism. Pharmacological inhibition or genetic loss of function of Lpar1 reduced the frequency of punctate junctions at sinus-lining LECs. Ligand activation of transfected LPAR1 in endothelial cells remodeled junctions from continuous to punctate structures and increased transendothelial permeability. In addition, LPAR1 antagonism in mice increased lymph node retention of adoptively transferred lymphocytes. These data suggest that cross-talk between LPAR1 and S1PR1 promotes the porous junctional architecture of sinus-lining LECs, which enables efficient lymphocyte trafficking. Heterotypic inter-GPCR coupling may regulate complex cellular phenotypes in physiological milieu containing many GPCR ligands.

01 Aug 2008·Arteriosclerosis, Thrombosis, and Vascular BiologyQ1 · MEDICINE

HDL-Associated Lysosphingolipids Inhibit NAD(P)H Oxidase-Dependent Monocyte Chemoattractant Protein-1 Production

Q1 · MEDICINE

Article

Author: Levkau, Bodo ; Pawlak, Alicja ; Tölle, Markus ; Lorkowski, Stefan ; Assmann, Gerd ; Kawamura, Akira ; Tietge, Uwe J. ; Schuchardt, Miriam ; Chun, Jerold ; Keul, Petra ; van der Giet, Markus ; Nofer, Jerzy-Roch

Objectives— High-density lipoprotein (HDL) levels are inversely proportional to the risk of atherosclerosis, but mechanisms of HDL atheroprotection remain unclear. Monocyte chemoatractant protein-1 (MCP-1) constitutes an early component of inflammatory response in atherosclerosis. Here we investigated the influence of HDL on MCP-1 production in vascular smooth muscle cells (VSMCs) and rat aortic explants. Methods and Results— HDL inhibited the thrombin-induced production of MCP-1 in a concentration-dependent manner. The HDL-dependent inhibition of MCP-1 production was accompanied by the suppression of reactive oxygen species (ROS), which regulate the MCP-1 production in VSMCs. HDL inhibited NAD(P)H oxidase, the preponderant source of ROS in the vasculature, and prevented the activation of Rac1, which precedes NAD(P)H-oxidase activation. The HDL capacity to inhibit MCP-1 production, ROS generation, and NAD(P)H-oxidase activation was emulated by sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), two lysosphingolipids present in HDL, but not by apolipoprotein A-I. HDL-, S1P-, and SPC-induced inhibition of MCP-1 production was attenuated in VSMCs pretreated with VPC23019, an antagonist of lysosphingolipid receptors S1P 1 and S1P 3 , but not by JTE013, an antagonist of S1P 2 . In addition, HDL, S1P, and SPC failed to inhibit MCP1 production and ROS generation in aortas from S1P 3 - and SR-B1-deficient mice. Conclusion— HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent ROS generation and MCP-1 production in a process that requires coordinate signaling through S1P 3 and SR-B1 receptors.

01 Apr 2001·British Journal of Pharmacology

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Article

Author: Martin C Michel ; Karl H Jakobs ; Angela Bischoff ; Dagmar Meyer zu Heringdorf

Lysosphingolipids such as sphingosine‐1‐phosphate (SPP) and sphingosylphosphorylcholine (SPPC) can act on specific G‐protein‐coupled receptors. Since SPP and SPPC cause renal vasoconstriction, we have investigated their effects on urine and electrolyte excretion in anaesthetized rats.

Infusion of SPP (1 – 30 μg kg−1 min−1) for up to 120 min dose‐dependently but transiently (peak after 15 min, disappearance after 60 min) reduced renal blood flow without altering endogenous creatinine clearance. Nevertheless, infusion of SPP increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis. These tubular lysosphingolipid effects developed more slowly (maximum after 60 – 90 min) and also abated more slowly upon lysosphingolipid washout than the renovascular effects.

Infusion of SPPC, sphingosine and glucopsychosine (3 – 30 μg kg−1 min−1 each) caused little if any alterations in renal blood flow but also increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis.

Pretreatment with pertussis toxin (10 μg kg−1 3 days before the acute experiment) abolished the renovascular and tubular effects of 30 μg kg−1 min−1 SPP.

These findings suggest that lysosphingolipids are a hitherto unrecognized class of endogenous modulators of renal function. SPP affects renovascular tone and tubular function via receptors coupled to Gi‐type G‐proteins. SPPC, sphingosine and glucopsychosine mimic only the tubular effects of SPP, and hence may act on distinct sites.

British Journal of Pharmacology (2001) 132, 1925–1933; doi:10.1038/sj.bjp.0703969

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