Distribution of endogenous farnesyl pyrophosphate and four species of lysophosphatidic acid in rodent brain.

Lysophosphatidic acid (LPA) is the umbrella term for lipid signaling molecules that share structural homology and activate the family of LPA receptors. Farnesyl Pyrophosphate (FPP) is commonly known as an intermediate in the synthesis of steroid hormones; however, its function as a signaling lipid is beginning to be explored. FPP was recently shown to an activator of the G-protein coupled receptor 92 (also known as LPA5) of the calcium channel TRPV(3). The LPA receptors (including GPR92) are associated with the signal transduction of noxious stimuli, however, very little is known about the distribution of their signaling ligands (LPAs and FPP) in the brain. Here, using HPLC/MS/MS, we developed extraction and analytical methods for measuring levels of FPP and 4 species of LPA (palmitoyl, stearoyl, oleoyl and arachidonoyl-sn-glycerol-3 phosphate) in rodent brain. Relative distributions of each of the five compounds was significantly different across the brain suggesting divergent functionality for each as signaling molecules based on where and how much of each is being produced. Brainstem, midbrain, and thalamus contained the highest levels measured for each compound, though none in the same ratios while relatively small amounts were produced in cortex and cerebellum. These data provide a framework for investigations into functional relationships of these lipid ligands in specific brain areas, many of which are associated with the perception of pain.