title: Nicotinamide inhibits inducible nitric oxide synthase enzyme activity in macrophages by allowing nitric oxide to inhibit its own formation.
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.
authors.affiliation: Laboratorio de Bioquímica de Sistemas Immunológicos, Departamento de Bioquímica Médica, Universidad de Sevilla, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Andrade
authors.forename: R
authors.initials: R
authors.lastname: Ramírez
authors.forename: M
authors.initials: M
authors.lastname: Conde
authors.forename: F
authors.initials: F
authors.lastname: Sobrino
authors.forename: F J
authors.initials: FJ
authors.lastname: Bedoya
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002956:Citrulline / Q000096:biosynthesis; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D009249:NADP / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D006454:Hemoglobins; D012333:RNA, Messenger; D001708:Biopterins; D009536:Niacinamide; D002956:Citrulline; D009569:Nitric Oxide; D009249:NADP; D019001:Nitric Oxide Synthase; C003402:sapropterin