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

FEBS Letters
C BogdanG Werner-Felmayer

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-gamma-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.

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Citations

Jul 25, 1998·Pharmacology & Toxicology·M IshiiT Yamamoto
Jan 1, 1997·Annual Review of Immunology·J MacMickingC Nathan
Feb 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Katrin WatschingerErnst R Werner
Jul 8, 2005·The Biochemical Journal·Galen M PieperJeannette Vásquez-Vivar
Jul 17, 2001·American Journal of Physiology. Heart and Circulatory Physiology·R S MarinosC J Meininger
Oct 5, 2002·Biological Research for Nursing·Brett M Mitchell, R Clinton Webb
Nov 21, 2002·Critical Care Medicine·Hong-Yun LiZhi-Yong C Y Sheng
Jan 1, 2014·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Petr JansaZdeněk Zídek
May 23, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Krishnasamy MamallanVelusamy Sethuraman
May 1, 2001·The Journal of Laboratory and Clinical Medicine·I F SchwartzA Iaina

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