Expression of lysophosphatidic acid receptor in rat astrocytes: mitogenic effect and expression of neurotrophic genes.

Lysophosphatidic acid (LPA) is a phospholipid mediator with a variety of biological activities. It remains unknown, however, which cells in the brain express the LPA receptor. The present study was undertaken to identify cells in the rat brain expressing functional LPA receptors, and to explore biological roles of LPA in these cells. We found that the LPA receptor was most dominantly expressed in rat astrocytes, determined by LPA-induced Ca2+ imaging, and by Northern blot analyses. LPA induced a mitogenic response and expression of immediate early genes in astrocytes, through pertussis-toxin sensitive G-protein(s). LPA also stimulated the expression of various cytokine genes, including nerve growth factor, interleukin (IL)-1beta, IL-3 and IL-6. Thus, astrocytes are the major target of LPA in the brain. We propose that LPA may play important roles in neuronal development, gliosis and wound-healing process in the brain.