title: Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations.
abstract: We studied the subcellular levels of melatonin in cerebral cortex and liver of rats under several conditions. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondrion vary over a 24-hr cycle, although these variations do not exhibit circadian rhythms. The cell membrane has the highest concentration of melatonin followed by mitochondria, nucleus, and cytosol. Pinealectomy significantly increased the content of melatonin in all subcellular compartments, whereas luzindole treatment had little effect on melatonin levels. Administration of 10 mg/kg bw melatonin to sham-pinealectomized, pinealectomized, or continuous light-exposed rats increased the content of melatonin in all subcellular compartments. Melatonin in doses ranging from 40 to 200 mg/kg bw increased in a dose-dependent manner the accumulation of melatonin on cell membrane and cytosol, although the accumulations were 10 times greater in the former than in the latter. Melatonin levels in the nucleus and mitochondria reached saturation with a dose of 40 mg/kg bw; higher doses of injected melatonin did not further cause additional accumulation of melatonin in these organelles. The results suggest some control of extrapineal accumulation or extrapineal production of melatonin and support the existence of regulatory mechanisms in cellular organelles, which prevent the intracellular equilibration of the indolamine. Seemingly, different concentrations of melatonin can be maintained in different subcellular compartments. The data also seem to support a requirement of high doses of melatonin to obtain therapeutic effects. Together, these results add information that assists in explaining the physiology and pharmacology of melatonin.
authors: Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain.
authors: Carmen
authors: C
authors: Venegas
authors: José A
authors: JA
authors: García
authors: Germaine
authors: G
authors: Escames
authors: Francisco
authors: F
authors: Ortiz
authors: Ana
authors: A
authors: López
authors: Carolina
authors: C
authors: Doerrier
authors: Laura
authors: L
authors: García-Corzo
authors: Luis C
authors: LC
authors: López
authors: Russel J
authors: RJ
authors: Reiter
authors: Darío
authors: D
authors: Acuña-Castroviejo
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000032:analysis* / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008550:Melatonin