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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: 15.98). 12/1995; 15(5):1003-15. DOI: 10.1016/0896-6273(95)90090-X
Source: PubMed

ABSTRACT 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.

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    • "The vSCN, but not the mSCN, expresses metabolic and electrical rhythmicity and receives retinohypothalamic (RHT) input. Further, the vSCN, but not the mSCN, contains melatonin receptor binding (Cassone et al., 1995; Lu and Cassone, 1993; Reppert et al., 1995; Rivkees et al., 1989), and exogenous melatonin inhibits metabolic activity in the vSCN (Lu and Cassone, 1993) but not in the mSCN. Finally , light activates c-fos expression in the vSCN, but not in the mSCN (King and Follett, 1997). "
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    ABSTRACT: In birds, biological clock function pervades all aspects of biology, controlling daily changes in sleep: wake, visual function, song, migratory patterns and orientation, as well as seasonal patterns of reproduction, song and migration. The molecular bases for circadian clocks are highly conserved, and it is likely the avian molecular mechanisms are similar to those expressed in mammals, including humans. The central pacemakers in the avian pineal gland, retinae and SCN dynamically interact to maintain stable phase relationships and then influence downstream rhythms through entrainment of peripheral oscillators in the brain controlling behavior and peripheral tissues. Birds represent an excellent model for the role played by biological clocks in human neurobiology; unlike most rodent models, they are diurnal, they exhibit cognitively complex social interactions, and their circadian clocks are more sensitive to the hormone melatonin than are those of nocturnal rodents.
    Frontiers in Neuroendocrinology 10/2013; DOI:10.1016/j.yfrne.2013.10.002 · 7.58 Impact Factor
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    • "These are G-protein-coupled receptors (GPCRs) (Reppert et al., 1995). Mel1a and Mel1c receptors are present in the LHRN (visual SCN) in the chicken brain (Reppert et al., 1995). Contrary to the melatonin rhythm, which is higher in the scotophase (dark period), [125I]-iodomelatonin binding in the brain is higher during the photophase and lower during the scotophase in chicken (Yuan and Pang, 1992), quail (Yuan and Pang, 1990), and pigeon (Yuan and Pang, 1991). "
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    ABSTRACT: Seasonally breeding birds detect environmental signals, such as light, temperature, food availability, and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction.
    Frontiers in Neuroscience 03/2013; 7:38. DOI:10.3389/fnins.2013.00038 · 3.70 Impact Factor
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    • "Rabbit polyclonal anti-X. laevis Mel1b receptor (Wiechmann et al., 2004) was raised against a peptide sequence (residues 221–233; VKSEFKPRMQSDF) with no identity to the corresponding region of the Xenopus Mel1a or Mel1c receptors (Reppert et al., 1995b) and affinity-purified as described previously (Wiechmann et al., 2004). Preincubation of the antibody with the inoculating peptide eliminates labeling and western blotting reveals a protein band of the appropriate size in Xenopus retinal tissue (Wiechmann et al., 2004). "
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    ABSTRACT: Melatonin receptors have been identified in several retinal cell types, including photoreceptors, horizontal cells, amacrine cells, and ganglion cells. Recent reports suggest that melatonin potentiates signaling from rods to inner retinal neurons. However, the organization of the melatonin receptors mediating this action in the outer plexiform layer (OPL) is not clear. To assess melatonin receptor localization in the OPL, double-label confocal immunohistochemistry for Mel1a or Mel1b melatonin receptors was performed in combination with markers for cone photoreceptors (calbindin, XAP-1) and ON bipolar cells (guanine nucleotide binding protein alpha, Goα) on the retina of Xenopus laevis. Both Mel1a and Mel1b receptors were specifically associated with processes contacting the pedicles of cones, but localized to processes from different sets of second-order neurons. Mel1a receptors localized to the large axonal processes of horizontal cells, while Mel1b receptors localized to the dendrites of OFF bipolar cells. Both receptors also localized to third-order amacrine and ganglion cells and their processes in the inner plexiform layer. This study indicates that Mel1a and Mel1b melatonin receptors are expressed specifically in the Xenopus OPL to modulate transmission from cones to horizontal cells and OFF bipolar cells, respectively; they are second-order neurons that predominantly contact ribbon synapses and display OFF responses to light. When combined with results from recent physiological studies, the current results suggest a conserved function for melatonin in enhancing transmission from rods to second-order neurons across species, although the precise mechanisms by which melatonin enhances this transmission are likely to vary in a species-dependent manner.
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