Melatonin: from biochemistry to therapeutic applications.
Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionary highly conserved molecule that plays an important role in conveying the clock and calendar information to all living organisms, including man. The hormone is synthesized mainly by the pineal gland, and, to a lesser extent, by extrapineal tissues--such as the retina, Harderian gland, and gastrointestinal tract. The melatonin-generating system is characterized by three basic features: (1) photosensitivity, (2) diurnal (or circadian) rhythmicity (with highest levels of the hormone production occurring at night in darkness), and (3) age-related decrease in its activity. This review surveys data on the regulation of rhythmic melatonin biosynthesis by an array of factors, such as circadian pacemaker, light, neurotransmitters, second and third messenger molecules. Recent developments in the field of melatonin receptors are also presented. Finally, physiological and therapeutic properties of melatonin, with a special emphasis given to possible applications of this compound in the treatment of circadian rhythm sleep disorders, are discussed.
Zawilska
J B
JB
Department of Biogenic Amines, Polish Academy of Sciences, Lódź, Poland.
Nowak
J Z
JZ
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D008027:Light; D008550:Melatonin / Q000096:biosynthesis / Q000494:pharmacology* / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000502:physiology; D018521:Plant Physiological Phenomena; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D044094:Receptors, Melatonin; D012621:Seasons; D012893:Sleep Wake Disorders / Q000188:drug therapy*
D000975:Antioxidants; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D008550:Melatonin