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Update on melatonin receptors: IUPHAR Review 20.

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TLDR
The current review provides an update on melatonin receptors by the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology, and highlights recent developments of melatonin receptor ligands, including radioligands, and gives anupdate on the latest phenotyping results ofmelatonin receptor knockout mice.
Abstract
Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including radioligands and give an update on the latest phenotyping results of melatonin receptor knockout mice. The current status and perspectives of the structure of melatonin receptor structures will be summarized. The physiological importance of melatonin receptor dimers and biologically important and type 2 diabetes-associated genetic variants of melatonin receptors will be discussed. The role of melatonin receptors in physiology and disease will be further exemplified by its functions in the immune system and the central nervous system. Finally, antioxidant and free radical scavenger properties of melatonin and its relation to melatonin receptors will be critically addressed.

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Journal ArticleDOI

Melatonin Synthesis and Function: Evolutionary History in Animals and Plants.

TL;DR: In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent.
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Melatonin as a hormone: new physiological and clinical insights

TL;DR: Maternal melatonin programs the fetuses' behavior and physiology to cope with the environmental light/dark cycle and season after birth, and unique ways of action turn melatonin into a biological time-domain-acting molecule.
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A brief review about melatonin, a pineal hormone

TL;DR: The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.
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Melatonin and Hippo Pathway: Is There Existing Cross-Talk?

TL;DR: The structure and functions of melatonin and its receptors are described, and both molecular and epidemiological evidence on melatonin anticancer effects are discussed, to shed light on potential cross-talk between melatonin signaling and the Hippo signaling pathway.
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Melatonin in type 2 diabetes mellitus and obesity

TL;DR: The rs10830963 single-nucleotide polymorphism (SNP) in the MTNR1B locus is associated with increased fasting plasma glucose levels and impaired insulin secretion, as well as increased risk of type 2 diabetes mellitus (T2DM) and gestational Diabetes mellitus.
References
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An integrated map of genetic variation from 1,092 human genomes

TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
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Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor

TL;DR: This article determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution and found that the highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the sevenhelix transmembrane motif.
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Structure of a nanobody-stabilized active state of the β2 adrenoceptor

TL;DR: A camelid antibody fragment to the human β2 adrenergic receptor is generated, and an agonist-bound, active-state crystal structure of the receptor-nanobody complex is obtained, providing insights into the process of agonist binding and activation.
Journal ArticleDOI

One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?

TL;DR: This review focuses on melatonin metabolism which includes the synthetic rate‐limiting enzymes, synthetic sites, potential regulatory mechanisms, bioavailability in humans, mechanisms of breakdown and functions of its metabolites.
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