D-aspartate uptake into cultured rat pinealocytes and the concomitant effect on L-aspartate levels and melatonin secretion.
Significant amounts of D-aspartate (Asp) are found in mammalian tissues and D-Asp is presumed to play some significant, but as yet undefined physiological role. However, it is not known whether D-Asp is synthesized in mammals. In this study, we addressed this issue in cultured rat pinealocytes, parenchymal cells of the pineal gland, which contain significant amounts of D-Asp. Biosynthesis of D-Asp was found to be minimal to non-existent in cultured rat pinealocytes. We then investigated the mechanism of uptake of D-Asp into these cells and its consequent effect on cell function. D-Asp was efficiently taken up into cells, in a time- and dose-dependent manner. Interestingly, the L-Asp levels in the cells and media decreased concomitantly with the uptake of D-Asp. This decrease was not due to D-Asp cytotoxicity, since the cellular levels of othernted. D-Serine and D-alanine were not taken up efficiently into the cells and the cellular levels of L-serine and L-alanine were unchanged. Also, immunocytochemical staining with anti-D-Asp antibody showed that D-Asp, which had been taken up into the cells, was dispersed throughout the cytoplasm. In response to norepinephrine stimulation, pinealocytes, which had been pretreated with D-Asp released D-Asp as well as L-Asp. In these cells, norepinephrine-induced secretion of melatonin, a pineal hormone, was suppressed. The mechanism of this suppression is discussed here.
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Y
Y
Takigawa
H
H
Homma
J A
JA
Lee
T
T
Fukushima
T
T
Santa
T
T
Iwatsubo
K
K
Imai
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D001224:Aspartic Acid; D008550:Melatonin; D009638:Norepinephrine