Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 7 October 1988:
Vol. 242. no. 4875, pp. 78 - 81
DOI: 10.1126/science.2845576
Prev | Table of Contents | Next

Articles

Science, Vol 242, Issue 4875, 78-81
Copyright © 1988 by American Association for the Advancement of Science

articles

Putative melatonin receptors in a human biological clock

SM Reppert, DR Weaver, SA Rivkees, and EG Stopa

Laboratory of Developmental Chronobiology, Boston.

In vitro autoradiography with 125I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific 125I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific 125I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific 125I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A three pulse phase response curve to three milligrams of melatonin in humans.
H. J. Burgess, V. L. Revell, and C. I. Eastman (2008)
J. Physiol. 586, 639-647
   Abstract »    Full Text »    PDF »
Melatonin and Human Chronobiology.
A. J. Lewy (2007)
Cold Spring Harb Symp Quant Biol 72, 623-636
   Abstract »    PDF »
Maternal Melatonin Effects on Clock Gene Expression in a Nonhuman Primate Fetus.
C. Torres-Farfan, V. Rocco, C. Monso, F. J. Valenzuela, C. Campino, A. Germain, F. Torrealba, G. J. Valenzuela, and M. Seron-Ferre (2006)
Endocrinology 147, 4618-4626
   Abstract »    Full Text »    PDF »
The therapeutic application of melatonin in supportive care and palliative medicine.
F. Mahmoud, N. Sarhill, and M. A. Mazurczak (2005)
American Journal of Hospice and Palliative Medicine 22, 295-309
   Abstract »    PDF »
Preferential Formation of MT1/MT2 Melatonin Receptor Heterodimers with Distinct Ligand Interaction Properties Compared with MT2 Homodimers.
M. A. Ayoub, A. Levoye, P. Delagrange, and R. Jockers (2004)
Mol. Pharmacol. 66, 312-321
   Abstract »    Full Text »    PDF »
Inhibition of Melatonin-Induced Ascorbic Acid and LHRH Release by a Nitric Oxide Synthase and Cyclic GMP Inhibitor.
S. Karanth, W. H. Yu, C. A. Mastronardi, and S. M. McCann (2004)
Experimental Biology and Medicine 229, 650-656
   Abstract »    Full Text »    PDF »
Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension.
F. A.J.L. Scheer, G. A. Van Montfrans, E. J.W. van Someren, G. Mairuhu, and R. M. Buijs (2004)
Hypertension 43, 192-197
   Abstract »    Full Text »    PDF »
Melatonin Acutely Improves the Neuroendocrine Architecture of Sleep in Blind Individuals.
S. Fischer, R. Smolnik, M. Herms, J. Born, and H. L. Fehm (2003)
J. Clin. Endocrinol. Metab. 88, 5315-5320
   Abstract »    Full Text »    PDF »
Developing Circadian Rhythmicity in Infants.
S. A. Rivkees (2003)
Pediatrics 112, 373-381
   Abstract »    Full Text »    PDF »
Monitoring of Ligand-independent Dimerization and Ligand-induced Conformational Changes of Melatonin Receptors in Living Cells by Bioluminescence Resonance Energy Transfer.
M. A. Ayoub, C. Couturier, E. Lucas-Meunier, S. Angers, P. Fossier, M. Bouvier, and R. Jockers (2002)
J. Biol. Chem. 277, 21522-21528
   Abstract »    Full Text »    PDF »
Seasonal Changes in Adiposity: the Roles of the Photoperiod, Melatonin and Other Hormones, and Sympathetic Nervous System.
T. J. Bartness, G. E. Demas, and C. K. Song (2002)
Experimental Biology and Medicine 227, 363-376
   Abstract »    Full Text »    PDF »
Postmortem Stability of Melatonin Receptor Binding and Clock-Relevant mRNAs in Mouse Suprachiasmatic Nucleus.
D. R. Weaver and C. E. Capodice (2001)
J Biol Rhythms 16, 216-223
   Abstract »    PDF »
Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats.
M. Nava, F. Romero, Y. Quiroz, G. Parra, L. Bonet, and B. Rodriguez-Iturbe (2000)
Am J Physiol Renal Physiol 279, F910-F918
   Abstract »    Full Text »    PDF »
Absence of Detectable Melatonin and Preservation of Cortisol and Thyrotropin Rhythms in Tetraplegia.
J. M. Zeitzer, N. T. Ayas, S. A. Shea, R. Brown, and C. A. Czeisler (2000)
J. Clin. Endocrinol. Metab. 85, 2189-2196
   Abstract »    Full Text »
Chimeric and Point-Mutated Receptors Reveal That a Single Glycine Residue in Transmembrane Domain 6 Is Critical for High Affinity Melatonin Binding.
A. K. Gubitz and S. M. Reppert (2000)
Endocrinology 141, 1236-1244
   Abstract »    Full Text »    PDF »
Serotonin 1A Receptors, Melatonin, and the Proportional Control Thermostat in Patients With Winter Depression.
P. J. Schwartz, N. E. Rosenthal, and T. A. Wehr (1998)
Arch Gen Psychiatry 55, 897-903
   Abstract »    Full Text »    PDF »
Cellular Mechanisms of Melatonin Action.
J. VANECEK (1998)
Physiol Rev 78, 687-721
   Abstract »    Full Text »    PDF »
Time and Time Again: The Phylogeny of Melatonin as a Transducer of Biological Time.
V. M. Cassone and A. K. Natesan (1997)
J Biol Rhythms 12, 489-497
   Abstract »    PDF »
Melatonin: Role in Development.
F. C. Davis (1997)
J Biol Rhythms 12, 498-508
   Abstract »    PDF »
Melatonin Receptors: Molecular Biology of a New Family of G Protein-Coupled Receptors.
S. M. Reppert (1997)
J Biol Rhythms 12, 528-531
   Abstract »    PDF »
The Effects of Evening Bright Light on Next-Day Sleep Propensity.
O. Tzischinsky and P. Lavie (1997)
J Biol Rhythms 12, 259-265
   Abstract »    PDF »
Melatonin in Humans.
A. Brzezinski (1997)
N. Engl. J. Med. 336, 186-195
   Full Text »    PDF »
Newborn primate infants are entrained by low intensity lighting.
S. A. Rivkees, P. L. Hofman, and J. Fortman (1997)
PNAS 94, 292-297
   Abstract »    Full Text »    PDF »
Melatonin and Light Induce Phase Shifts of Circadian Activity Rhythms in the C3H/HeN Mouse.
S. Benloucif and M. L. Dubocovich (1996)
J Biol Rhythms 11, 113-125
   Abstract »    PDF »
Light Treatment for Sleep Disorders: Consensus Report: II. Basic Properties of Circadian Physiology and Sleep Regulation.
D.-J. Dijk, Z. Boulos, C. I. Eastman, A. J. Lewy, S. S. Campbell, and M. Terman (1995)
J Biol Rhythms 10, 113-125
   Abstract »    PDF »
The Pineal Gland: Photoreception and Coupling of Behavioral, Metabolic, and Cardiovascular Circadian Outputs.
W. S. Warren and V. M. Cassone (1995)
J Biol Rhythms 10, 64-79
   Abstract »    PDF »
Influence of Acute Melatonin Treatment and Light on the Circadian Melatonin Rhythm in the Djungarian Hamster.
S. M. Yellon and S. Hilliker (1994)
J Biol Rhythms 9, 71-81
   Abstract »    PDF »
Circadian and Photoperiodic Time Measurement in Male Syrian Hamsters Following Lesions of the Melatonin-Binding Sites of the Paraventricular Thalamus.
F. J. P. Ebling, E. S. Maywood, T. Humby, and M. H. Hastings (1992)
J Biol Rhythms 7, 241-254
   Abstract »    PDF »
The Pineal Gland Influences Rat Circadian Activity Rhythms in Constant Light.
V. M. Cassone (1992)
J Biol Rhythms 7, 27-40
   Abstract »    PDF »
Melatonin Administration to Blind People: Phase Advances and Entrainment.
R. L. Sack, A. J. Lewy, M. L. Blood, J. Stevenson, and L. D. Keith (1991)
J Biol Rhythms 6, 249-261
   Abstract »    PDF »
The Visual Input Stage of the Mammalian Circadian Pacemaking System: I. Is There a Clock in the Mammalian Eye?.
C. E. Reme, A. Wirz-Justice, and M. Terman (1991)
J Biol Rhythms 6, 5-29
   Abstract »    PDF »
Bright light induction of strong (type 0) resetting of the human circadian pacemaker.
C. Czeisler, R. Kronauer, J. Allan, J. Duffy, M. Jewett, E. Brown, and J. Ronda (1989)
Science 244, 1328-1333
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)