LPA receptor signaling: pharmacology, physiology, and pathophysiology

Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

“…Importantly, the stimulation of cells by exosomes was not solely through signalling of LPAR1, LPAR2 and LPAR3 because the promotion of DNA synthesis was insensitive to Ki16425. Although it remains possible that LPAR4, LPAR5 and LPAR6, which also activate a range of Gprotein-mediated signalling pathways (Yung et al, 2014), could be responsible for stimulating DNA synthesis in cells, it is more likely to be due to growth factors, such as EGF, that are known to be carried by exosomes (Record et al, 2011). In contrast, exosomestimulated cell migration in a scratch wound assay was absolutely dependent upon LPAR1, LPAR2 and LPAR3.…”

Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain

“…LPA (1-acyl-2-sn-glycerol-3-phosphate) is a wellcharacterised glycerophospholipid with a molecular weight of approximately 430-480 Dalton (Yung et al, 2014). LPA activates a family of six distinct G protein-coupled receptors (GPCRs), named LPA is generated by a number of different enzymes such as phospholipases A 1 and A 2 , monoacylglycerol kinase, glycerol-3-phosphate acyltransferase and autotaxin (ATX) (Noguchi et al, 2009;Pebay et al, 2007) from various precursors including phosphatidic acid, glycerol-3-phosphate M A N U S C R I P T…”

“…LPA can be produced by platelets (Eichholtz et al, 1993), fibroblasts (Fukami and Takenawa, 1992), mitotic neurons (Fukushima et al, 2000), astrocytes (Savaskan et al, 2007) and also cancer cells (Zhao et al, 2010). High concentrations of LPA have been observed in several pathological conditions such as atherosclerosis (Smyth et al, 2014), traumatic brain injury (Crack et al, 2014), spinal cord injury (Santos- Nogueira et al, 2015), different types of cancer (Eder et al, 2000;Lee and Yun, 2010;Zeng et al, 2009;Zhao et al, 2010), neuropsychiatric disorders (Yung et al, 2014) and neuropathic pain (Ahn et al, 2009;Fujita et al, 2007). Production of LPA during inflammation promotes wound-healing and acts to control the proinflammatory environment.…”

Plant Lysophosphatidic Acids: A Rich Source for Bioactive Lysophosphatidic Acids and Their Pharmacological Applications

“…However, with the discovery of LPA receptor subtypes in various animal organs, most organs have been found to express LPA receptors including organs in the nervous system, cardiovascular system, immune system, and endocrine and reproductive system. 1) In each organ, LPA plays an important role for cell proliferation, migration, division and survival. However, the availability of endogenous LPA in animal cells or body fluids is very low because of its low concentration.…”

“…1) They are synthesized from glycerol, with fatty acids and a phosphate group conjugated to the glycerol backbone. Lysophosphatidic acids (LPAs) are one of the simplest of all glycerophospholipids.…”