2,4-DIAMINO-6-HYDROXYPYRIMIDINE, AN INHIBITOR OF TETRAHYDROBIOPTERIN SYNTHESIS, DOWN-REGULATES THE EXPRESSION OF INOS PROTEIN AND MESSENGER-RNA IN PRIMARY MURINE MACROPHAGES

被引：29

作者：

BOGDAN, C ^{[1
]}

WERNER, E ^{[1
]}

STENGER, S ^{[1
]}

WACHTER, H ^{[1
]}

ROLLINGHOFF, M ^{[1
]}

WERNERFELMAYER, G ^{[1
]}

机构：

[1] UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA

来源：

FEBS LETTERS | 1995年 / 363卷 / 1-2期

关键词：

2,4-DIAMINO-6-HYDROXY-PYRIMIDINE; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRIC OXIDE; TETRAHYDROBIOPTERIN; GTP CYCLOHYDROLASE I;

D O I：

10.1016/0014-5793(95)00284-G

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：69 / 74

页数：6