l-Glutamate in the extracellular space regulates endogenous d-aspartate homeostasis in rat pheochromocytoma MPT1 cells

• Published in: Archives of biochemistry and biophysics 2004-04, Vol.424 (1), p.89-96
• Main Authors: Adachi, Minako, Koyama, Hayato, Long, Zhiqun, Sekine, Masae, Furuchi, Takemitsu, Imai, Kazuhiro, Nimura, Noriyuki, Shimamoto, Keiko, Nakajima, Terumi, Homma, Hiroshi
• Format: Article
• Language: English
• Subjects: Amino Acid Transport System X-AG - antagonists & inhibitors; Amino Acid Transport System X-AG - metabolism; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Aspartic Acid - pharmacology; Cell Line, Tumor; Cysteine - analogs & derivatives; Cysteine - metabolism; Cysteine - pharmacology; d-Aspartate; dl-TBOA; Extracellular Space - metabolism; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Homeostasis; l-Glutamate transporter; Neurotransmitter Agents; PC12 Cells; Pheochromocytoma - metabolism; Rat pheochromocytoma cells; Rats
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2004.01.016

In previous studies [FEBS Lett. 434 (1998) 231, Arch. Biochem. Biophys. 404 (2002) 92], we demonstrated for the first time that d-aspartate ( d-Asp) is synthesized in cultured mammalian cell lines, such as pheochromocytoma 12 (PC12) and its subclone, MPT1. Our current focus is analysis of the dynamics of d-Asp homeostasis in these cells. In this communication, we show that l-glutamate (Glu) and l-Glu transporter substrates in the extracellular space regulate the homeostasis of endogenous d-Asp in MPT1 cells. d-Asp is apparently in dynamic homeostasis, whereby endogenous d-Asp is constantly released into the extracellular space by an undefined mechanism, and continuously and intensively taken up into cells by an l-Glu transporter. Under these conditions, l-Glu and its transporter substrates in the medium may competitively inhibit the uptake of d-Asp via the transporter, resulting in accumulation of the amino acid in the extracellular space. We additionally demonstrate that dl-TBOA, a well-established l-Glu transporter inhibitor, is taken up by the transporter during long time intervals, but not on a short time-scale.