Melatonin and its receptors: biological function in circadian sleep–wake regulation

摘要: Biosynthesis and metabolism of melatonin Melatonin was isolated in 1958 by Lerner his associates, its chemical nature being identified as N -acetyl-5-methoxytryptamine (Lerner et al . 1958, 1959) (Fig. 10.1). In vertebrates, is primarily secreted the pineal gland. Synthesis also occurs other cells organs including retina (Cardinali Rosner 1971; Tosini Menaker 1998; Liu 2004), human murine bone marrow (Conti 2000), platelets (Champier 1997), gastrointestinal tract (Bubenik 2002), skin (Slominski 2005a,b), or lymphocytes (Carrillo-Vico 2004). However, circulating derived only from gland, shown disappearance after removal. Since there no storage since degraded rapidly liver, plasma levels reflect biosynthetic activity. secretion synchronized to light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) low diurnal baseline (about 10 plasma). Studies have supported value exogenous administration circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders immune function, oxidative damage (Karasek 2002; Pandi-Perumal 2005, 2006; Srinivasan 2005a,b, Hardeland 2006).