Understanding melatonin receptor pharmacology: Latest insights from mouse models, and their relevance to human disease

Abstract

Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models.

Rola błonowych receptorów melatoniny w zależnym od melatoniny uwalnianiu oksytocyny z układu podwzgórze-część nerwowa przysadki szczura — badania in vitro oraz in vivo

“…Melatonin membrane receptors are coupled to a variety of G-proteins, so acting through these receptors, melatonin can produce multiple cellular responses [40][41]. Activation of MT 1 receptor may, therefore, result in inhibition of the cyclic adenosine monophosphate (cAMP)-dependent signal transduction cascade, including decreases in protein kinase A (PKA) activity and nuclear factor CREB (cAMP responsive elementbinding protein) phosphorylation.…”

“…Activation of MT 1 receptor may, therefore, result in inhibition of the cyclic adenosine monophosphate (cAMP)-dependent signal transduction cascade, including decreases in protein kinase A (PKA) activity and nuclear factor CREB (cAMP responsive elementbinding protein) phosphorylation. It may also induce a phospholipase C (PLC)-dependent signal transduction cascade with protein kinase C (PKC) activation and elevation of cytosolic free calcium ions accumulation [15,18,[41][42][43]. Acting through MT 1 receptor, melatonin can also elicit other tissue-dependent signalling responses, including modulation of different specific ion channels (e.g.…”

“…Acting through MT 1 receptor, melatonin can also elicit other tissue-dependent signalling responses, including modulation of different specific ion channels (e.g. potassium channels) and/or regulation of a variety of kinases activity [15][16]41]. As mentioned above, our results indicate that the stimulatory effect of pharmacological dose of melatonin on OT secretion from the rat H-N system is, probably, independent of both subtypes MT 1 and MT 2 receptors and involves other, i.e.…”

Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5‐methylcytosine

“…Melatonin is a ubiquitous molecule present in almost every organism from bacteria to humans . It is involved in sleep and circadian rhythms, antioxidant activity, and immunity enhancement .…”

Pathophysiology of Depression: Molecular Regulation of Melatonin Homeostasis – Current Status

“…Depending on the cellular context, homo- and heteromeric complexes of melatonin receptors can be formed. Recruitment of various G proteins and regulatory proteins to these complexes further differentiates the receptor signaling capacity [39]. Additionally, receptor gene variants may cause receptor expression and function as well as increase the risk of disease and affect drug efficacy.…”