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CAT2 arginine transporter deficiency significantly reduces iNOS‐mediated NO production in astrocytes
Author(s) -
Manner Cathyryne K.,
Nicholson Benjamin,
MacLeod Carol L.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01695.x
Subject(s) - nitric oxide , nitric oxide synthase , astrocyte , arginine , transporter , pathogenesis , chemistry , pharmacology , microbiology and biotechnology , biology , biochemistry , endocrinology , medicine , central nervous system , amino acid , gene
We have previously demonstrated that genetic ablation of cationic amino acid transporter 2 ( Cat2 ) significantly inhibits nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in activated macrophages. Here we report that iNOS activity is impaired by 84% in activated Cat2 ‐deficient astrocytes. Cat2 ablation appears to reduce astrocyte NO synthesis by decreasing the uptake of the sole precursor, arginine, as well as by reducing the expression of iNOS following activation. Excessive or dysregulated NO production by activated astrocytes and other CNS cell types has been implicated in the pathogenesis of neurological disorders. Our results support the idea that manipulation of CAT2 transporter function might be useful for the therapeutic modulation of iNOS activity.