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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Arendt, J. Melatonin and the Mammalian Pineal Gland (Chapman and Hill, London, 1995).
Reppert, S. M. J. Biol. Rhythms 12, 528–531 (1997).
Reppert, S. M. Weaver, D. R. & Ebisawa, T. Neuron 13, 1177–1185 (1994).
Reppert, S. M. et al. Proc. Natl. Acad. Sci. USA 12, 8734–8738 (1995).
Liu, C. et al. Neuron 19, 91–102 (1997).
Costa, E. Annu. Rev. Pharmacol. Toxicol. 38, 321–350 (1998).
Macdonald, R. L. & Olsen, R. W. Annu. Rev. Neurosci. 17, 569–602 (1994).
Reppert, S. M. & Weaver, D. R. Cell 89, 487–490 (1997).
Ralph, M. R. & Menaker, M. J. Neurosci. 9, 2858–2865 (1989).
Wagner, S., Castel, M., Gainer, H. & Yarom, Y. Nature 387, 598–603 (1997).
Oaknin-Bendahan, S., Anis, Y., Nir, I. & Zisapel, N. J. Basic Clin. Physiol. Pharmacol. 3, 253–268 (1992).
Weaver, D. R. & Reppert, S. M. Neuroreport 20, 109–112 (1996).
Dubocovich, M. L., Yun, K., Al-Ghoul, W. M., Benloucif, S. & Masana, M. I. FASEB J. 12, 1211–1220 (1998).
Conway, S. et al. FEBS Lett. 407, 121–126 (1997).
Wilsbacher, L. D. & Takahashi, J. S. Curr. Opin. Genet. Dev. 8, 595–602 (1998).
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wan, Q., Man, HY., Liu, F. et al. Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat Neurosci 2, 401–403 (1999). https://doi.org/10.1038/8062
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/8062
This article is cited by
-
Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders
Translational Psychiatry (2021)
-
Adjuvant use of melatonin for relieving symptoms of painful diabetic neuropathy: results of a randomized, double-blinded, controlled trial
European Journal of Clinical Pharmacology (2021)
-
Rivastigmine patch (Exelon patch) compared to melatonin patch in prevention of postoperative delirium in the elderly
Ain-Shams Journal of Anesthesiology (2020)
-
Melatonin and Multiple Sclerosis: From Plausible Neuropharmacological Mechanisms of Action to Experimental and Clinical Evidence
Clinical Drug Investigation (2019)
-
Circadian rhythm in melatonin release as a mechanism to reinforce the temporal organization of the circadian system in crayfish
Invertebrate Neuroscience (2017)