L-Glutamate in the extracellular space regulates endogenous D-aspartate homeostasis in rat pheochromocytoma MPT1 cells.
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.
Adachi
Minako
M
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Koyama
Hayato
H
Long
Zhiqun
Z
Sekine
Masae
M
Furuchi
Takemitsu
T
Imai
Kazuhiro
K
Nimura
Noriyuki
N
Shimamoto
Keiko
K
Nakajima
Terumi
T
Homma
Hiroshi
H
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis; D018377:Neurotransmitter Agents; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats
D027322:Amino Acid Transport System X-AG; D018377:Neurotransmitter Agents; C120673:benzyloxyaspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D003545:Cysteine; C013461:cysteine sulfinic acid