2,4‐diamino‐6‐hydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis, downregulates the expression of iNOS protein and mRNA in primary murine macrophages

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Abstract
2,4‐diamino‐6‐hydroxy‐pyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, blocks the synthesis of tetrahydrobiopterin (BH4), 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 BH4‐independent manner and, thus, acts by a novel mechanism.