Regional distribution and postnatal changes of d-amino acids in rat brain

Hamase, Kenji; Homma, Hiroshi; Takigawa, Yuki; Fukushima, Takeshi; Santa, Tomofumi; Imai, Kazuhiro

doi:10.1016/s0304-4165(96)00095-5

Cited by 166 publications

(138 citation statements)

References 30 publications

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“…D-Alanine is the first D-amino acid found in serum of guinea pig and mice [16]. Subsequent studies demonstrated that free D-alanine is one of the D-amino acids naturally occurring in the mammalian tissues including brain and blood [17][18][19][20][21][22]. D-Alanine, like D-serine, is also a selective and potent agonist at the glycine-modulatory site on the NMDA receptors [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Effects of D-Amino Acid Oxidase Inhibitor on the Extracellular D-Alanine Levels and the Efficacy of D-Alanine on Dizocilpine-Induced Prepulse Inhibition Deficits in Mice

Horio¹,

Fujita²,

Ishima³

et al. 2009

TOCCHEMJ

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D-Alanine, one of D-amino acids present in the mammalian brain, is a selective and potent agonist at the Nmethyl-D-aspartate (NMDA) receptors. Like D-serine, D-alanine is reported to be effective in the treatment of schizophrenia. However, orally given D-alanine is metabolized substantially by D-amino acid oxidase (DAAO), diminishing its oral bioavailability. In this study, we studied the effects of oral D-alanine administration with or without the novel DAAO inhibitor, 5-chloro-benzo[d]isoxazol-3-ol (CBIO), on the extracellular D-alanine levels in the brain and on the prepulse inhibition (PPI) deficits after administration of the NMDA receptor antagonist dizocilpine. Co-administration of CBIO (30 mg/kg) with D-alanine (100 mg/kg), but not D-alanine (100 mg/kg) alone, significantly attenuated dizocilpine (0.1 mg/kg)-induced PPI deficits in mice. The in vivo microdialysis study of the conscious and free moving mice revealed that co-administration of CBIO (30 mg/kg) significantly increased extracellular levels of D-alanine in the frontal cortex after oral administration of D-alanine (100 mg/kg). These findings suggest that co-administration of CBIO can increase the bioavailability of D-alanine after oral administration of D-alanine, and that co-administration of CBIO can enhance the efficacy of D-alanine on dizocilpine-induced PPI deficits. Therefore, combination of D-alanine and a DAAO inhibitor such as CBIO offers new therapeutic potential for treatment of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Effects of D-Amino Acid Oxidase Inhibitor on the Extracellular D-Alanine Levels and the Efficacy of D-Alanine on Dizocilpine-Induced Prepulse Inhibition Deficits in Mice

Horio¹,

Fujita²,

Ishima³

et al. 2009

TOCCHEMJ

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“…NBD-F derivatization was basically carried out according to the method described by Hamase et al ( 19 ). Briefly, the sample (20 L) was mixed with 40 L of 0.2 M boric acid buffer (pH 8.0) and 60 L of 50 m M NBD-F in acetonitrile.…”

Section: Methodsmentioning

confidence: 99%

Content of Free D-Ala and D-Glu in Traditional Asian Fermented Seasonings

Mori

Ito

Nagasawa

2010

J Nutr Sci Vitaminol

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Summary Free D -amino acids have increasingly attracted attention due to their physiological roles and pathological effects on animals, including humans. In this study, using a chiral high-performance liquid chromatography system, we determined free D -amino acids, particularly D -Ala and D -Glu, in traditional seasonings of four soy sauces, three misos, and four fish sauces that are commonly used in Asian cuisine. Examination of the average contents of the free D -amino acids in all the samples revealed that the content of D -Ala was 3.6 times higher than that of free D -Glu, while the average content of free L -Ala was lower (0.8 times) than that of free L -Glu. The average content of free L -Ala was significantly higher in the soy sauces (53 mol/g sample) and fish sauces (53 mol/g sample) than in the misos (14 mol/g sample), whereas the average content of free D -Ala was almost equal among the soy sauces, misos, and fish sauces (0.25, 0.29, and 0.23 mol/g sample, respectively). Taken together, neither free D -Ala nor D -Glu content showed a correlation with its free Lform in the samples, suggesting that the D -enantiomers are not necessarily produced by the same factors as those for the L -enantiomers, which originate from raw materials. Thus, factors specific to the production process of the fermented seasonings appear to play a significant role in their enantiomer content. Key Words fermented seasonings, free amino acids, D -amino acids, D -alanine, D -glutamic acid Amino acids are essential nutrients for all living organisms. Each amino acid except glycine has one asymmetric center at the ␣ carbon atom and is composed of L -and D -enantiomers. Racemic mixtures of Land D -amino acids are synthesized by several organic reactions in vitro. However, most living organisms except microorganisms predominantly use L -amino acids. It remains a scientific mystery why the L -configuration was selected by higher living systems, while microorganisms can produce, utilize, and metabolize Damino acids, possessing 30 to 50% of their free amino acids as D -enantiomers ( 1 , 2 ). Microorganisms especially use D -Ala and D -Glu as essential constituents of their cell wall peptidoglycans, which contribute to the protection of the cell wall against digestive attack by proteolysis enzymes ( 3 ).Little attention has been paid to the physiological and biological roles of D -amino acids in mammals due to their limited utilization. However, with advances in the analytical methodologies that can quantify trace levels of amino acid enantiomers, free D -amino acids have been found in a wide variety of mammalian tissues, including those of humans ( 4 , 5 ). High-dose administration of some D -amino acids, including D -Glu, to experimental animals has been reported to induce several deleterious physiological effects ( 6 ). On the other hand, D -Ser has been detected in the frontal brain regions ( 7 , 8 ) and has been revealed to function as a neuromodulator in the central nervous system ( 9 , 10 ). D -Ala has also been demonstrated to fu...

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“…As described above, a large amount of D-Ser (ca. 300 nmol/g tissue) is observed in the frontal brain, 7,[17][18][19] and this D-amino acid is now recognized as an endogenous neuromodulator. [8][9][10] D-Asp is widely present in the endocrine tissues (higher than 100 nmol/g tissue) 18,20,21 and its physiological function in regulating hormonal synthesis and secretion has gradually been clarified.…”

Section: Two-dimensional Hplc Determination Of Small Amounts Of D-amimentioning

confidence: 99%

Analysis of Small Amounts of d-Amino Acids and the Study of Their Physiological Functions in Mammals

et al. 2009

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D-Amino acids, the enantiomers of L-amino acids, are candidates to be novel physiologically active substances and the biomarkers in mammals. However, the amounts of D-amino acids in the tissues and physiological fluids are extremely small in most cases, and sensitive and selective analytical methods are needed for their determination. In the present manuscript, we review the analytical technologies including our recent advances for the determinations of small amounts of D-amino acids in mammals and the applications to clarify their physiological meanings.

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Regional distribution and postnatal changes of d-amino acids in rat brain

Cited by 166 publications

References 30 publications

Effects of D-Amino Acid Oxidase Inhibitor on the Extracellular D-Alanine Levels and the Efficacy of D-Alanine on Dizocilpine-Induced Prepulse Inhibition Deficits in Mice

Effects of D-Amino Acid Oxidase Inhibitor on the Extracellular D-Alanine Levels and the Efficacy of D-Alanine on Dizocilpine-Induced Prepulse Inhibition Deficits in Mice

Content of Free D-Ala and D-Glu in Traditional Asian Fermented Seasonings

Analysis of Small Amounts of d-Amino Acids and the Study of Their Physiological Functions in Mammals

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