1 By the late 1960s, researchers had become aware that this somewhat obscure class of lipids had the remarkable ability to act like an extracellular signaling molecule.2 Two prominent forms typify but do not limit lysophospholipids: lysophosphatidic acid (LPA), which is derived from glycerophospholipids such as phosphatidyl serine or phosphatidyl choline (known commonly as lecithin, as in egg yolk); and sphingosine 1-phosphate (S1P), which is derived from sphingolipids such as sphingomyelin, ceramide, and sphingosine.
Although rare compared to most membrane lipids, they could be found in relatively high concentrations (micromolar) within blood plasma and/or serum. How these lysophospholipids worked was unclear and much debated in the decade preceding the mid-1990s, with explanations invoking lysophospholipids as membrane disruptors (lysophospholipids look a bit like detergents), second messengers, ionophores, calcium chelators, as well as ligands for intracellular and extracellular receptors.
"We had found a gene and the GPCR it encoded, ...
