Abstract
Nitric oxide (NO) production by macrophages is mainly regulated by induction of nitric oxide synthase (iNOS) by cytokines and microbial products. Nicotinamide (NIC) inhibits NO production by activated macrophages in a dose dependent manner. NIC also inhibits NOS enzyme activity in extracts from activated macrophages. The inhibition was noncompetitive with L-arginine (Ki 13.37 +/- 4.40 mM, n=3), uncompetitive versus NADPH (Ki 3.06 +/- 0.17 mM, n=3) and tetrahydrobiopterin. Finally, the inhibition by nicotinamide was fully reversed by scavenging NO with hemoglobin. We suggest that NIC acts by allowing NO to inhibit its own formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biopterins / analogs & derivatives
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Biopterins / metabolism
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Citrulline / biosynthesis
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Female
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Hemoglobins / metabolism
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Macrophages, Peritoneal / drug effects*
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Macrophages, Peritoneal / enzymology
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Macrophages, Peritoneal / metabolism
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Male
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Mice
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NADP / metabolism
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Niacinamide / pharmacology*
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Nitric Oxide / biosynthesis
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Nitric Oxide / physiology*
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase / genetics
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RNA, Messenger / genetics
Substances
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Hemoglobins
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RNA, Messenger
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Biopterins
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Niacinamide
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Citrulline
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Nitric Oxide
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NADP
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Nitric Oxide Synthase
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sapropterin