TY - JOUR
T1 - Changes in d-aspartic acid and d-glutamic acid levels in the tissues and physiological fluids of mice with various d-aspartate oxidase activities
AU - Han, Hai
AU - Miyoshi, Yurika
AU - Koga, Reiko
AU - Mita, Masashi
AU - Konno, Ryuichi
AU - Hamase, Kenji
N1 - Funding Information:
This work was partly supported by JSPS KAKENHI Grant Number 25293007 and 26860023 , Japan. The authors thank Shiseido Co., Ltd., (Tokyo, Japan) for their technical supports. The authors also thank Professors Solomon H. Snyder (The Johns Hopkins University School of Medicine), Stephen G. Young, Anne Beigneux (University of California) and their co-workers for their kindly providing the DDO-KO mouse materials and suggestions.
PY - 2015/12/10
Y1 - 2015/12/10
N2 - d-Aspartic acid (d-Asp) and d-glutamic acid (d-Glu) are currently paid attention as modulators of neuronal transmission and hormonal secretion. These two d-amino acids are metabolized only by d-aspartate oxidase (DDO) in mammals. Therefore, in order to design and develop new drugs controlling the d-Asp and d-Glu amounts via regulation of the DDO activities, changes in these acidic d-amino acid amounts in various tissues are expected to be clarified in model animals having various DDO activities. In the present study, the amounts of Asp and Glu enantiomers in 6 brain tissues, 11 peripheral tissues and 2 physiological fluids of DDO+/+, DDO+/- and DDO-/- mice were determined using a sensitive and selective two-dimensional HPLC system. As a result, the amounts of d-Asp were drastically increased with the decrease in the DDO activity in all the tested tissues and physiological fluids. On the other hand, the amounts of d-Glu were almost the same among the 3 strains of mice. The present results are useful for designing new drug candidates, such as DDO inhibitors, and further studies are expected.
AB - d-Aspartic acid (d-Asp) and d-glutamic acid (d-Glu) are currently paid attention as modulators of neuronal transmission and hormonal secretion. These two d-amino acids are metabolized only by d-aspartate oxidase (DDO) in mammals. Therefore, in order to design and develop new drugs controlling the d-Asp and d-Glu amounts via regulation of the DDO activities, changes in these acidic d-amino acid amounts in various tissues are expected to be clarified in model animals having various DDO activities. In the present study, the amounts of Asp and Glu enantiomers in 6 brain tissues, 11 peripheral tissues and 2 physiological fluids of DDO+/+, DDO+/- and DDO-/- mice were determined using a sensitive and selective two-dimensional HPLC system. As a result, the amounts of d-Asp were drastically increased with the decrease in the DDO activity in all the tested tissues and physiological fluids. On the other hand, the amounts of d-Glu were almost the same among the 3 strains of mice. The present results are useful for designing new drug candidates, such as DDO inhibitors, and further studies are expected.
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U2 - 10.1016/j.jpba.2015.05.013
DO - 10.1016/j.jpba.2015.05.013
M3 - Article
C2 - 26058797
AN - SCOPUS:84945470668
SN - 0731-7085
VL - 116
SP - 47
EP - 52
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -