title: N-nitrosomelatonin enhances photic synchronization of mammalian circadian rhythms.
abstract: Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse at circadian time 18 generated a twofold increase of locomotor rhythm phase-advances, having no effect over saturating light pulses. This potentiation was also obtained even when inhibiting suprachiasmatic nitric oxide synthase activity. However, N-nitrosomelatonin had no effect on light-induced phase delays at circadian time 14. The photic-enhancing effects were correlated with an increased suprachiasmatic immunoreactivity of FBJ murine osteosarcoma viral oncogene and period1. Moreover, in vivo nitric oxide release by N-nitrosomelatonin was verified by measuring nitrate and nitrite levels in suprachiasmatic nuclei homogenates. The compound also accelerated resynchronization to an abrupt 6-h advance in the light:dark cycle (but not resynchronization to a 6-h delay). Here, we demonstrate the chronobiotic properties of N-nitrosomelatonin, emphasizing the importance of nitric oxide-mediated transduction for circadian phase advances.
authors.affiliation: Laboratorio de Cronobiología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes/CONICET, Bernal, Argentina.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Baidanoff
authors.forename: Santiago A
authors.initials: SA
authors.lastname: Plano
authors.forename: Fabio
authors.initials: F
authors.lastname: Doctorovich
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Suárez
authors.forename: Diego A
authors.initials: DA
authors.lastname: Golombek
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Chiesa
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D006224:Cricetinae; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008647:Mesocricetus; D009043:Motor Activity / Q000502:physiology; D009603:Nitroso Compounds; D010775:Photic Stimulation / Q000379:methods*; D017440:Photoperiod; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
chemical_list: C503522:N1-nitrosomelatonin; D009603:Nitroso Compounds; D008550:Melatonin
keywords: N-nitrosomelatonin; circadian; jet lag; nitric oxide; suprachiasmatic nucleus