Reppert SM, Weaver DR, Cassone VM, et al. Melatonin receptor are for the birds: molecular analysis of two receptor subtypes differentially expressed in chick brain. Neuron 15: 1003-15

Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Neuron (Impact Factor: 15.05). 12/1995; 15(5):1003-15. DOI: 10.1016/0896-6273(95)90090-X
Source: PubMed


Two receptors (CKA and CKB) of the G protein-coupled melatonin receptor family were cloned from chick brain. CKA encodes a protein that is 80% identical at the amino acid level to the human Mel1a melatonin receptor and is thus designated the chick Mel1a melatonin receptor. CKB encodes a protein that is 80% identical to the Xenopus melatonin receptor and defines a new receptor subtype, the Mel1c melatonin receptor, which is distinct from the Mel1a and Mel1b melatonin receptor subtypes. A melatonin receptor family consisting of three subtypes is supported by PCR cloning of distinct melatonin receptor fragments from Xenopus and zebrafish. Expression of CKA and CKB results in similar ligand binding and functional characteristics. The widespread distribution of CKA and CKB mRNA in brain provides a molecular substrate for the profound actions of melatonin in birds.

    • "The locations and pharmacology of melatonin receptors have recently been extensively reviewed. Two cloned receptors, MT1 and MT2 (Masana and Dubocovich, 2001;Reppert et al., 1995), are of particular importance with regard to rhythm physiology and pharmacology. Using gene knockout technology in mice and pharmacological manipulations, the results to date suggest that the phase-shifting melatonin receptor in the SCN is MT2, while MT1 is associated with acute suppression of SCN electrical activity (Liu et al., 1997). "
    Article: Melatonin
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    ABSTRACT: Melatonin (N-acetyl-5-methoxytryptamine) is synthesised largely in the pineal gland at night with a marked circadian rhythm, driven by a central 'clock' the suprachiasmatic nuclei of the hypothalamus. Light suppresses production and synchronises the rhythm to 24. h. Melatonin signals time of day and time of year to body physiology by its profile of secretion. This signal is used to time seasonal functions e.g. reproduction, coat growth, timing of puberty in photoperiodic species, via melatonin receptors on the pars tuberalis of the pituitary stalk. Endogenous melatonin reinforces the functioning of the human circadian system, notably sleep and the core body temperature rhythm. In large doses and in vitro it has anti-oxidant and neuroprotective properties. The melatonin rhythm is the best peripheral index of the timing of the human circadian 'clock.' Exogenous melatonin acts as a 'chronobiotic' and a soporific, acting, at least in part, via melatonin receptors in the SCN. Agonists and antagonists to melatonin receptors MT1 and MT2, have been developed. It has been most successful as a timed treatment for circadian rhythm related sleep disorders.
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    • "In addition, two subtypes of Mtnr1a, i.e. Mtnr1a1.4 (also known as Mel 1a 1.4) and Mtnr1a1.7 (also known as Mel 1a 1.7), have been identified in zebrafish, Danio rerio (Reppert et al., 1995), rainbow trout, Oncorhynchus mykiss (Mazurais et al., 1999), grass puffer, Takifugu niphobles (Ikegami et al., 2009b), and goldfish, Carassius auratus (Ikegami et al., 2009a). The mudskipper Boleophthalmus pectinirostris, a burrow-dwelling fish inhabiting intertidal mudflats, is an exceptional model among fishes for their amphibious behavior and numerous physiological and morphological specializations adapted for amphibious life (Chen et al., 2006, 2007; Hong et al., 2007, 2013). "
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    • "Melatonin may have direct and indirect effects. Most of the avian brain is sensitive to melatonin, as shown by the widespread distribution of melatonin receptors in almost all brain regions of several birds species [44-46] including Sylvia warblers (Fusani & Gahr, unpublished). Thus, it is conceivable the melatonin acts directly on some area to suppress (or reduce) Zugunruhe by influencing circadian oscillators [5,47]. "
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    ABSTRACT: A remarkable aspect of bird migration is its nocturnality, particularly common in Passeriformes. The switch in activity from purely diurnal to also nocturnal is evident even in caged birds that during migratory periods develop an intense nocturnal restlessness, termed Zugunruhe. The mechanisms that control this major change in activity are mostly unknown. Previous work with Sylvia warblers suggested an involvement of melatonin, a hormone associated with day-night cycles in most vertebrates. In a recent study we found no effects of melatonin administration on Zugunruhe during spring migration. However, previous studies indicated that the response to melatonin manipulation could differ between spring and autumn migration, which are in fact separate life history stages. Here we tested whether a non-invasive treatment with melatonin can alter Zugunruhe in wild garden warblers S. borin and blackcaps S. atricapilla subject to temporary captivity at an autumnal stopover site. Food availability in the cage (yes/no) was added as a second factor because previous work showed that it enhanced Zugunruhe. The melatonin treatment significantly decreased the amount of Zugunruhe, while the availability of food only tended to increase the amount of Zugunruhe. Fuel deposits also had a strong effect on the amount of nocturnal activity: lean birds with a fat score of 1 showed significantly less Zugunruhe than fatter birds. The change in body mass during the time spent in the recording cage depended on food availability, but not on any of the other factors. This study shows that the migratory programme of two Sylvia warblers can be manipulated by administration of exogenous melatonin and confirms that this hormone is involved in the control of migratory behaviour. To our knowledge, this is one of the first demonstrations that the autumn migratory programme can be altered by hormonal manipulation in migrating birds. The comparison with a similar study carried out with the same modalities during spring migration suggests that there are seasonal differences in the sensitivity of the migratory programme to hormonal factors. In birds breeding in the northern hemisphere, the importance of a timely arrival to the breeding sites could explain why the control of the migratory programme is more rigid in spring.
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