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Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors

Nature Neuroscience volume 2, pages 401403 (1999) | Download Citation

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Abstract

Melatonin, a hormone principally produced and released by the pineal gland, has been shown to regulate a variety of biological functions including circadian rhythms, sleep-wake cycles and reproduction1, presumably through activating high-affinity G-protein-coupled receptors2,3,4,5. We report here that these subtypes can differentially modulate the function of type-A γ-aminobutyric acid (GABAA) receptor, the principal neurotransmitter receptor mediating synaptic inhibition in the CNS6,7. This work demonstrates that melatonin, through activation of different receptor subtypes, can exert opposite effects on the same substrate, suggesting that receptor subtype is the primary molecular basis for the diversity of melatonin effects.

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Acknowledgements

We thank C. Kaufman and D. Gunnersen at the Laboratory of Neuroscience, NIDDK, for providing us with GABAA receptor subunit cDNAs and S. M. Reppert at Harvard Medical School for human Mel1a and Mel1b cDNAs. This work was supported by grants from the Medical Research Council of Canada, the Heart and Stroke Foundation of Ontario and the Fealdman Memorial Fund (to Y.T.W.), the Clarke Foundation (to G.M.B.) and the Neuroendocrinology Research Fund (to S.F.P.). Q.W. is a Canadian MRC Fellow, H.B.N is a Career Scientist of the Ontario Ministry of Health, and Y.T.W. is a Research Scholar of the Heart and Stroke Foundation of Canada.

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Affiliations

  1. Brain and Behaviour Program, Research Institute and Department of Pediatric Laboratory Medicine, Hospital for Sick Children, and Department of Laboratory Medicine and Pathobiology, University of Toronto, McMaster Building, Room 5018F, 555 University Ave., Toronto, Ontario M5G 1X8, Canada

    • Qi Wan
    • , Heng-Ye Man
    • , Jodi Braunton
    •  & Yu Tian Wang
  2. Clarke Institute of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada

    • Qi Wan
    • , Fang Liu
    • , Hyman B. Niznik
    • , Shiu Fun Pang
    •  & Gregory M. Brown
  3. Department of Physiology, The University of Hong Kong, 5 Sassoon Road, Hong Kong

    • Shiu Fun Pang

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Correspondence to Yu Tian Wang.

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DOI

https://doi.org/10.1038/8062

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