Lysophosphatidic acid-induced itch is mediated by signalling of LPA5receptor, phospholipase D and TRPA1/TRPV1 DOI Open Access

Hiroki Kittaka,

Kunitoshi Uchida,

Naomi Fukuta

et al.

The Journal of Physiology, Journal Year: 2017, Volume and Issue: 595(8), P. 2681 - 2698

Published: Feb. 8, 2017

Key points Lysophosphatidic acid (LPA) is an itch mediator, but not a pain mediator by cheek injection model. Dorsal root ganglion neurons directly respond to LPA depending on transient receptor potential ankyrin 1 (TRPA1) and vanilloid (TRPV1). LPA‐induced itch‐related behaviours are decreased in TRPA1‐knockout (KO), TRPV1KO or TRPA1TRPV1 double KO mice. TRPA1 TRPV1 channels activated intracellular LPA, extracellular following 5 activation with activity of Ca 2+ ‐independent phospholipase A 2 D. Intracellular interaction sites KK672–673 KR977–978 (K: lysine, R: arginine). Abstract Intractable continuous sensations often accompany diseases such as atopic dermatitis, neurogenic lesions, uremia cholestasis. found cholestatic patients it induces acute experimental rodent models. However, the molecular mechanism which activates peripheral sensory remains unknown. In this study, we used method mice reveal that induced pain‐related behaviours. The behaviour cellular effects were dependent (TRPV1), important for signal transduction. We also that, among six receptors, had greatest involvement itching. Furthermore, demonstrated D (PLD) plays critical role downstream intracellularly TRPV1. These results suggest unique cytoplasmic produced de novo could activate conclude mediated , PLD, signalling, thus targeting TRPA1, PLD be effective interventions.

Language: Английский

Illuminating G-Protein-Coupling Selectivity of GPCRs DOI Creative Commons
Asuka Inoue, Francesco Raimondi, Francois Marie Ngako Kadji

et al.

Cell, Journal Year: 2019, Volume and Issue: 177(7), P. 1933 - 1947.e25

Published: June 1, 2019

Language: Английский

Citations

547
Emerging roles of lysophospholipids in health and disease DOI Creative Commons
Shu Ting Tan, T. Ramesh, Xiu Ru Toh

et al.

Progress in Lipid Research, Journal Year: 2020, Volume and Issue: 80, P. 101068 - 101068

Published: Oct. 14, 2020

Lipids are abundant and play essential roles in human health disease. The main functions of lipids building blocks for membrane biogenesis. However, also metabolized to produce signaling molecules. Here, we discuss the emerging circulating lysophospholipids. These lysophospholipids consist lysoglycerophospholipids lysosphingolipids. They both present cells at low concentration, but their concentrations extracellular fluids significantly higher. biological some these have been recently revealed. Remarkably, pivotal as well being precursors Revealing how produced, released, transported, utilized multi-organ systems is critical understand functions. discovery enzymes, carriers, transporters, receptors has shed light on physiological significance. In this review, summarize via discussing about proteins regulating We potential impacts diseases.

Language: Английский

Citations

255
Lysophosphatidic Acid Signaling in the Nervous System DOI Creative Commons
Yun C. Yung,

Nicole C. Stoddard,

Hope Mirendil

et al.

Neuron, Journal Year: 2015, Volume and Issue: 85(4), P. 669 - 682

Published: Feb. 1, 2015

Language: Английский

Citations

235
Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets DOI
Minh Thiet Vu,

Ayako-Nakamura Ishizu,

Juat Chin Foo

et al.

Nature, Journal Year: 2017, Volume and Issue: 550(7677), P. 524 - 528

Published: Oct. 1, 2017

Language: Английский

Citations

218
Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies DOI Creative Commons
Luiz Henrique Geraldo, Tânia Cristina Leite de Sampaio e Spohr, Rackele Ferreira do Amaral

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 1, 2021

Abstract Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and pathological conditions. Here, we review the literature about differential signaling of LPA through its specific receptors, which makes this lipid a versatile molecule. This important for understanding how molecule can have such diverse effects during central nervous system angiogenesis; also, it act as powerful mediator conditions, neuropathic pain, neurodegenerative diseases, cancer progression. Ultimately, preclinical clinical uses Autotaxin, LPA, receptors therapeutic targets, approaching most recent data promising molecules modulating production signaling. aims to summarize update knowledge mechanisms order understand biological health disease.

Language: Английский

Citations

207
Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1 DOI Creative Commons

Jill Chrencik,

C. Roth,

Masahiko Terakado

et al.

Cell, Journal Year: 2015, Volume and Issue: 161(7), P. 1633 - 1643

Published: June 1, 2015

Language: Английский

Citations

199
Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis DOI Creative Commons
William J. Sandborn, Laurent Peyrin‐Biroulet, Jinkun Zhang

et al.

Gastroenterology, Journal Year: 2019, Volume and Issue: 158(3), P. 550 - 561

Published: Nov. 9, 2019

Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod patients with moderately to severely active ulcerative colitis (UC).In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, endoscopy findings) 4-9, endoscopic subscores 2 or more, bleeding 1 more were randomly assigned groups given once-daily mg (n = 52), 50), placebo 54) 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers 17 countries. primary endpoint increase mean improvement MCS baseline week 12. Secondary endpoints included proportion (subscores less) Exploratory endpoints, including clinical remission, are reported article, although statistically powered draw conclusions only on endpoint.At 12, group met all secondary endpoints. led significantly greater than (difference placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P .009), 0.43 points (90% reduction 0.24 1.11; nominal .15). Endoscopic occurred 41.8% receiving vs 17.8% (P .003). Most adverse events mild moderate. Three had transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously evidence before exposure.In colitis, effective producing improvements. Further warranted. Clinicaltrials.gov, Number: NCT02447302.

Language: Английский

Citations

189
The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives DOI Creative Commons
Andrea Huwiler,

Uwe Zangemeister‐Wittke

Pharmacology & Therapeutics, Journal Year: 2017, Volume and Issue: 185, P. 34 - 49

Published: Nov. 8, 2017

Language: Английский

Citations

188
Sphingosine 1-phosphate and sphingosine kinases in health and disease: Recent advances DOI
Susan Pyne, David R. Adams, Nigel J. Pyne

et al.

Progress in Lipid Research, Journal Year: 2016, Volume and Issue: 62, P. 93 - 106

Published: March 9, 2016

Language: Английский

Citations

170
Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives DOI Creative Commons
Gary Álvarez Bravo,

René Robles Cedeño,

Marc Puig Casadevall

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2058 - 2058

Published: June 29, 2022

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are bioactive lipid molecules that ubiquitously expressed in the human body play an important role immune system. S1P-S1PR signaling has been well characterized trafficking activation both innate adaptive systems. Despite this knowledge, full scope pathogenesis of autoimmune disorders is not yet. From discovery fingolimod, first modulator, until siponimod, new molecule recently approved for treatment secondary progressive multiple sclerosis (SPMS), there a great advance understanding functions their involvement diseases, including (MS). Modulation on interesting target various disorders. Improved mechanism action fingolimod allowed development more selective second-generation S1PR modulators. Subtype 1 (S1PR1) cell surface lymphocytes, which known to major MS pathogenesis. The S1PR1’s facilitated pharmacological strategies directed target, theoretically reduced safety concerns derived from use fingolimod. A was achieved March 2019 when Food Drug Association (FDA) Siponimod, active relapsing–remitting MS. Siponimod became oral disease modifying therapy (DMT) specifically forms Additionally, relapsing MS, ozanimod by FDA 2020. Currently, ongoing trials focused other new-generation S1PR1 This review approaches fundamental aspects sphingosine phosphate modulators main similarities differences.

Language: Английский

Citations

81