title: Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.
abstract: The ergot alkaloid bromocriptine (BKT) was found to act as a strong inhibitor of purified neuronal nitric oxide synthase (NOS) (IC50 = 10 +/- 2 microM) whereas it was poorly active towards inducible macrophage NOS (IC50 > 100 microM). BKT affects the activation of NOS by calmodulin, as it not only inhibits L-arginine oxidation to NO and L-citrulline but also NADPH oxidation and calmodulin-dependent cytochrome c reduction catalyzed by neuronal NOS. These results suggest that BKT could exert some of its therapeutic effects by interfering with the NOS-dependent formation of nitric oxide and/or superoxide ion in various tissues.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Renodon
authors.forename: J L
authors.initials: JL
authors.lastname: Boucher
authors.forename: M A
authors.initials: MA
authors.lastname: Sari
authors.forename: M
authors.initials: M
authors.lastname: Delaforge
authors.forename: J
authors.initials: J
authors.lastname: Ouazzani
authors.forename: D
authors.initials: D
authors.lastname: Mansuy
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D001971:Bromocriptine / Q000494:pharmacology*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009249:NADP / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D001971:Bromocriptine; D009249:NADP; D019001:Nitric Oxide Synthase