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Cited by 451

The DOI matches its Crossref record; 125 of the 125 references it cites were found in a registry or an index.

Molecular pharmacology regulation and function of mammalian melatonin receptors

Open access
Dubocovich, Margarita L·2003·Frontiers in Bioscience
DOI 10.2741/1089
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Abstract

Melatonin (5-methoxy-N-acetyltryptamine), dubbed the hormone of darkness, is released following a circadian rhythm with high levels at night. It provides circadian and seasonal timing cues through activation of G protein-coupled receptors (GPCRs) in target tissues (1). The discovery of selective melatonin receptor ligands and the creation of mice with targeted disruption of melatonin receptor genes are valuable tools to investigate the localization and functional roles of the receptors in native systems. Here we describe the pharmacological characteristics of melatonin receptor ligands and their various efficacies (agonist, antagonist, or inverse agonist), which can vary depending on tissue and cellular milieu. We also review melatonin-mediated responses through activation of melatonin receptors (MT1, MT2, and MT3) highlighting their involvement in modulation of CNS, hypothalamic-hypophyseal-gonadal axis, cardiovascular, and immune functions. For example, activation of the MT1 melatonin receptor inhibits neuronal firing rate in the suprachiasmatic nucleus (SCN) and prolactin secretion from the pars tuberalis and induces vasoconstriction. Activation of the MT2 melatonin receptor phase shifts circadian rhythms generated within the SCN, inhibits dopamine release in the retina, induces vasodilation, enhances splenocyte proliferation and inhibits leukocyte rolling in the microvasculature. Activation of the MT3 melatonin receptor reduces intraocular pressure and inhibits leukotriene B4-induced leukocyte adhesion. We conclude that an accurate characterization of melatonin receptors mediating specific functions in native tissues can only be made using receptor specific ligands, with the understanding that receptor ligands may change efficacy in both native tissues and heterologous expression systems.

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Metadata

Authors
Dubocovich, M. L.
Venue
Frontiers in Bioscience
Publisher
IMR Press
Published
2003
Volume
8
Issue
4
Pages
d1093-1108
ISSN
  • 1093-4715 (ISSN-L)
  • 1093-9946
DOI
10.2741/1089
OpenAlex
W1594539812
Cited by
451
References
125
FWCI
8.18
Type
journal article
Language
en
Open access
bronze

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