Melatonin, role

Lavie, P. (1997). Melatonin role in gating nocturnal rise in sleep propensity. J. Biol Rhythms 12, 657-65. 

Figure 22.1 Pathways projecting to and from the suprachiasmatic nucleus (SCN). Inputs from photoreceptors in the retina help to reset the circadian clock in response to changes in the light cycle. Other inputs derive from the lateral geniculate complex and the serotonergic, Raphe nuclei and help to reset the SCN in response to non-photic stimuli. Neurons in the SCN project to the hypothalamus, which has a key role in the regulation of the reproductive cycle, mood and the sleep-waking cycle. These neurons also project to the pineal gland which shows rhythmic changes in the rate of synthesis and release of the hormone, melatonin...

The precise role of melatonin in sleep and waking is uncertain but it seems to act as a go-between for the light and biological cycles and evidence suggests that it has a reciprocal relationship with the SCN (Fig. 22.3). Its actions are mediated by (MLi) receptors which are found predominantly in the SCN as well as thalamic nuclei and the anterior pituitary. These are G protein-coupled receptors, with seven transmembrane domains, that inhibit adenylyl cyclase. Their activation by melatonin, or an MLi agonist such as 2-iodomelatonin, restores the impaired circadian cycle in aged rats. 

Doyle S., Grace M., Mclvor W. (2002). Menaker M. Circadian rhythms of dopamine in mouse retina the role of melatonin. Vis. Neurosci. 19, 593-601. 

One of us examined the timely use of three factors (melatonin treatment, exposure to light, physical exercise) to hasten the resynchronization of the sleep-wake cycle in a group of elite sports competitors after a transmeridian flight across 12 time zones (Cardinali et al. 2002). Outdoor light exposure and physical exercise were used to cover symmetrically the phase delay and the phase advance portions of the phase-response curve. Melatonin taken at local bedtime helped to resynchronize the circadian oscillator to the new time. Individual actograms taken from sleep log data showed that all subjects became synchronized in their sleep to the local time in 24-48 h, well in advance of what would be expected in the absence of any treatment (Cardinali et al. 2002). More recently, a retrospective analysis of the data obtained from 134 normal volunteers flying the Buenos Aires - Sydney transpolar route in the past 9 years was published this further supports such a role for exogenous melatonin in resynchronization of sleep cycles (Cardinal et al. 2006). 

Carrillo-Vico, A., Calvo, J. R., Abreu, P. el al. (2004). Evidence of melatonin synthesis by human lymphocytes and its physiological significance possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 18, 537-9. 

Esquifino, A. I., Pandi-Perumal, S. R. Cardinali, D. P. (2004). Circadian organization of the immune response A role for melatonin. Clin. Appl. Immunol Rev. 4, 423-33. 

Ali, S.F., Martin, J.L., Black, M.D., Itzhak, Y. Neuroprotective role of melatonin in methamphetamine-and l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity. Ann. N.Y. Acad. Sci. 890 119, 1999. 

HT is metabolized by the action of monoamine oxidase by a process of oxidative deamination to yield 5-hydroxyindoleacetic acid (5-HIAA). In the pineal gland, 5-HT is o-methylated to form melatonin. While the physiological importance of this transmitter in the regulation of the oestrus cycle in ferrets would appear to be established, its precise role in man is unknown. Nevertheless, it has been speculated that melatonin plays some... 

In addition to its presumed role as a neurotransmitter within the brain, serotonin is synthesized in the pineal gland, where it is a precursor for the synthesis of melatonin, a hormone that influences endocrine activity, presumably by an action within the hypothalamus. 

Wide distribution also occurs in metabolites that play the same role in phylogenetically and ecologicafiy distant organisms, like peptides of the endothelin class (Chart 8.1.A/P), defensive monoterpenoids and steroids, the gibberellins (diterpenoid hormones) (Chart 8.1.1), and the alkaloid melatonin. 

Reiter RJ, Melchiorri D, Sewerynek E A review of the evidence supporting melatonin s role as an antioxidant. J Pineal Res 18 1-11, 1995 Reiter SR, Pollack S, Rosenbaum JF, et al Clonazepam for the treatment of social phobia. J Chn Psychiatry 51 470-472, 1990 Remington G, Adams M Risperidone and obsessive-compulsive symptoms [letter. ... 

Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia assessment in a clinical trial of melatonin replacement. Sleep 1998 21 52-68. 

Serotonin is present in a variety of sites in the brain. Its role as a neurotransmitter and its relation to the actions of drugs acting in the central nervous system are discussed in Chapters 21 and 30. Serotonin is also a precursor of melatonin in the pineal gland (Figure 16-2 ... 

Melatonin is /V-acetyl-5-methoxytryptamine (Figure 16-2), a simple methoxylated and /V-acetylated product of serotonin found in the pineal gland. It is produced and released primarily at night and has long been suspected of playing a role in diurnal cycles of animals and the sleep-wake behavior of humans. 

Melatonin is found in many areas of many animals. It is involved in the skin coloration of amphibians, and in the thermal or motor regulation in some higher animals. Its major regulatory role is in response to light and, in man, is the major hormone produced by the pineal gland. 

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