title: Changes in D-aspartic acid and D-glutamic acid levels in the tissues and physiological fluids of mice with various D-aspartate oxidase activities.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Han
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Miyoshi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Koga
authors.affiliation: Shiseido Co., Ltd., 1-6-2 Higashi-shimbashi, Minato-ku, Tokyo 105-8310, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mita
authors.affiliation: Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8501, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Konno
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: hamase@phar.kyushu-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamase
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D050804:D-Aspartate Oxidase / Q000032:analysis / Q000378:metabolism*; D026603:D-Aspartic Acid / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D026603:D-Aspartic Acid; D050804:D-Aspartate Oxidase
keywords: Chiral analysis; Two-dimensional HPLC; d-Aspartate oxidase; d-Aspartic acid; d-Glutamic acid