QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.077123v1 312/3/1090    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xin, Y.-F. Articles by Wang, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Xin, Y.-F. Articles by Wang, Y.-X. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SODIUM BENZOATE

ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Renal D-Amino Acid Oxidase Mediates Chiral Inversion of N^G-Nitro-D-arginine

Laboratory of Pharmacology, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China

N^G-nitro-D-arginine (D-NNA), i.v. injected into rats, produced a pressor response, and was presumed to act via chiral inversion into N^G-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. We examined the possible role of renal D-amino acid oxidase (DAAO) in the chiral inversion of D-NNA to L-NNA. In pentobarbital-anesthetized rats, L-NNA was detected via capillary electrochromatography in the blood immediately after i.v. injection of D-NNA. The time course of appearance of L-NNA paralleled the increase in blood pressure elicited by D-NNA. Unilateral renal ligation partially, and bilateral ligation completely, blocked the pressor response as well as the conversion of D-NNA to L-NNA. Furthermore, injection into conscious rats of sodium benzoate, a selective DAAO inhibitor, completely blocked the pressor response to naive D-NNA, but not pressor response to D-NNA preincubated with homogenates of the kidney. Homogenates of the kidneys, liver (lesser degree), and brain (much lesser degree) converted D-NNA to L-NNA, and the chiral inversion was blocked by the addition of benzoate. Moreover, D-NNA chiral inversion correlates with the activity of DAAO. Our results reveal a novel pathway of chiral inversion of D-amino acids where the renal DAAO plays an essential role that accounts for the biological activity of D-NNA.

Address correspondence to: Dr. Yong-Xiang Wang, Laboratory of Pharmacology, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China. E-mail: yxwang{at}sjtu.edu.cn

This article has been cited by other articles:

				X. Yan-Fei, Z. Xiang-Jun, L. Jie, and W. Yong-Xiang Inhibitory Effects of Benzoate on Chiral Inversion and Clearance of NG-Nitro-Arginine in Conscious Rats Drug Metab. Dispos., March 1, 2007; 35(3): 331 - 334. [Abstract] [Full Text] [PDF]