Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.
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.
Renodon
A
A
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Paris, France.
Boucher
J L
JL
Sari
M A
MA
Delaforge
M
M
Ouazzani
J
J
Mansuy
D
D
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
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D001971:Bromocriptine; D009249:NADP; D019001:Nitric Oxide Synthase