ACCELERATED COMMUNICATION Characterization of a Receptor Subtype-Selective Lysophosphatidic Acid Mimetic

Despite an intriguing cell biology and the suggestion of a role in pathophysiological responses, the mechanism of action of such lipid phosphoric acid mediators as lysophosphatidic acid (LPA) remains obscure, in part because of an underdeveloped medicinal chemistry. We report now the agonist activity of a synthetic phospholipid in which the glycerol backbone of LPA is replaced by L-serine. Like LPA, the L-serine-based lipid mo-bilizes calcium and inhibits activation of adenylyl cyclase in the human breast cancer cell line MDA MB231. Treatment with LPA desensitizes MDA MB231 cells to subsequent application of the L-serine compound; when the order of application is re-versed, however, the L-serine compound does not prevent calcium mobilization by LPA, which might indicate the exis-tence of two LPA receptors in these cells. The analogou