RT info:eu-repo/semantics/article
T1 Inhibition of neuronal nitric oxide synthase activity by N1‐acetyl‐5‐methoxykynuramine, a brain metabolite of melatonin
A1 León, Josefa
A1 Escames, Germaine
A1 Rodríguez, María I.
A1 López, Luis C.
A1 Tapias, Víctor
A1 Entrena, Antonio
A1 Camacho, Encarnación
A1 Carrión, María D.
A1 Gallo, Miguel A.
A1 Espinosa, Antonio
A1 Tan, Dun‐Xian
A1 Reiter, Russel J.
A1 Acuña Castroviejo, Darío
AB We assessed the effects of melatonin, N(1)-acetyl-N (2)-formyl-5-methoxykynuramine (AFMK) and N(1)-acetyl-5-methoxykynuramine (AMK) on neuronal nitric oxide synthase (nNOS) activity in vitro and in rat striatum in vivo. Melatonin and AMK (10(-11)-10(-3) m), but not AFMK, inhibited nNOS activity in vitro in a dose-response manner. The IC(50) value for AMK (70 microm) was significantly lower than for melatonin (>1 mm). A 20% nNOS inhibition was reached with either 10(-9) m melatonin or 10(-11) m AMK. AMK inhibits nNOS by a non-competitive mechanism through its binding to Ca(2+)-calmodulin (CaCaM). The inhibition of nNOS elicited by melatonin, but not by AMK, was blocked with 0.05 mm norharmane, an indoleamine-2,3-dioxygenase inhibitor. In vivo, the potency of AMK to inhibit nNOS activity was higher than that of melatonin, as a 25% reduction in rat striatal nNOS activity was found after the administration of either 10 mg/kg of AMK or 20 mg/kg of melatonin. Also, in vivo, the administration of norharmane blocked the inhibition of nNOS produced by melatonin administration, but not the inhibition produced by AMK. These data reveal that AMK rather than melatonin is the active metabolite against nNOS, which may be inhibited by physiological levels of AMK in the rat striatum.
SN 0022-3042
YR 2006
FD 2006
LK https://uvadoc.uva.es/handle/10324/63870
UL https://uvadoc.uva.es/handle/10324/63870
LA eng
NO Journal of Neurochemistry, Septiembre 2006, vol. 98, n. 6, p. 2023-2033
NO Producción Científica
DS UVaDOC
RD 17-jul-2024