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2,4‐diamino‐6‐hydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis, downregulates the expression of iNOS protein and mRNA in primary murine macrophages
Author(s) -
Bogdan Christian,
Werner Ernst,
Stenger Steffen,
Wachter Helmut,
Rbllinghoff Martin,
Werner-Felmayer Gabriele
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00284-g
Subject(s) - tetrahydrobiopterin , gtp cyclohydrolase i , nitric oxide synthase , nitric oxide , chemistry , cofactor , messenger rna , cytokine , microbiology and biotechnology , biochemistry , biology , enzyme , immunology , organic chemistry , gene
2,4‐diamino‐6‐hydroxy‐pyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, blocks the synthesis of tetrahydrobiopterin (BH 4 ), which is a known cofactor of inducible nitric oxide synthase (iNOS). Previously, DAHP was shown to suppress the production of nitric oxide by cytokine‐activated fibroblasts, smooth muscle cells or endothelial cells which could be attributed to its function as a cofactor antagonist. Here, we demonstrate that in interferon‐γ‐activated murine peritoneal macrophages DAHP suppresses the expression of iNOS mRNA and protein in a BH 4 ‐independent manner and, thus, acts by a novel mechanism.