Cell density inversely regulates d- and l-aspartate levels in rat pheochromocytoma MPT1 cells

In a previous report (FEBS Lett. 434 (1998) 231), we demonstrated for the first time that d-aspartate (d-Asp) is synthesized in rat pheochromocytoma 12 (PC12) cells. This unique amino acid is believed to act as a novel messenger in mammalian cell regulation. However, the dynamics of d-Asp homeostasis in mammalian cells is yet to be elucidated. In this communication, we demonstrate that d-Asp is also synthesized in MPT1 cells (a subclone of PC12 cells) and that the d- and l-Asp levels in cells are regulated by cell density of the culture. Our data show that d-Asp levels increase, while in contrast, l-Asp levels decrease as a function of increased cell density. Conversely, in PC12 cells, which do not express the glutamate transporter involved in the incorporation of d- and l-Asp into cells, l-Asp levels decrease upon cell density increase while d-Asp concentrations remain almost unchanged. The results indicate that the biochemical behaviors of d- and l-Asp in mammalian cells are distinct and that the cellular levels of these stereoisomers appear to be under different control mechanisms.