Search

OBJECTIVE: Melatonin regulates the mammalian circadian rhythm and plays metabolic functions such as glucose homeostasis. Both melatonin receptors (MTNR1A and MTNR1B, encoded by the MTNR1A and MTNR1B genes, respectively) are expressed in pancreatic beta cells and mediate the glucometabolic roles of melatonin as well as insulin secretion. The MTNR1B gene is a well-known genetic risk factor in type 2 diabetes (T2D); however, little is known about the involvement of the MTNR1A gene in here T2D. We aimed to investigate whether MTNR1A is linked to and/or associated with familial T2D. SUBJECTS AND METHODS: We genotyped 14 single nucleotide polymorphisms within the MTNR1A gene in 212 peninsular Italian families with T2D. We performed parametric linkage and linkage disequilibrium analyses to investigate the role of MTNR1A variants in conferring T2D risk. We considered variants statistically significant if conferring linkage or linkage disequilibrium with p < 0.05. RESULTS: We found 3 novel variants (rs62350392, rs2119883, and rs13147179) significantly linked to and/or associated with T2D in multigenerational Italian families. CONCLUSIONS: This is the first study to report MTNR1A as a novel risk gene in T2D. Functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the sleep-promoting effects of corn leaf extract (UP165) and its active component 6-methoxybenzoxazolinone (6-MBOA), along with the underlying mechanisms in rodent models. Sleep activity in UP165 was measured by measuring sleep duration in the pentobarbital induced sleep model, and sleep quality was evaluated through electroencephalogram (EEG) analysis. In addition, the sleep mechanism was analyzed through an in vivo sleep study co-administrated with receptor antagonists. The administrations of both UP165 and 6-MBOA effectively increased sleep duration, demonstrating a 3-fold increase sleep time at 100 mg/kg UP165 and a 2.3-fold increase at 280 μg/kg 6-MBOA compared to those of the control group. The sleep-promoting effect of UP165 was also observed in the caffeine-induced insomnia model, resulting in a 71.6% increase in sleep duration. The UP165-mediated increase in sleep time was attributed to enhanced non-rapid eye movement (NREM) sleep, specifically an increase in the δ-wave sleep measured by EEG. Mechanism analysis with co-administration of competitive antagonists in vivo revealed that UP165 and 6-MBOA enhanced sleep duration through binding to gamma-aminobutyric acid type A (GABA A) and melatonin receptors. Oral administration of UP165 for 4 weeks effectively increased both gene expression and protein levels of GABA A , melatonin 1A, and melatonin 1B receptors. High-dose administration of UP165 significantly decreased the blood level of corticosterone, while concurrently increased GABA, serotonin, and melatonin levels in brain. This study highlights the potential of UP165 and 6-MBOA as edible-grade natural ingredients for sleep promotion. [Display omitted] [ABSTRACT FROM AUTHOR]

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan–Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour–node–metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019–1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development. [ABSTRACT FROM AUTHOR]

To obtain greater knowledge of the extra-pineal sources of melatonin during development, the amount of indolamine and the expression levels of the last two enzymes involved in its biosynthesis, Arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT), were analyzed in the human thymus from children from three different age groups (from days to years). The melatonin membrane and nuclear receptor expression levels also were studied. Quantitative reverse transcriptase PCR and western blot were performed to investigate the receptor and enzyme expression levels. The results were examined and correlated with the ages of the thymuses. We found high levels of indolamine in the thymuses of newborns (younger than 1 month), which decreased during development; thymuses from the months (from 2 to 11 months) and years (from 1 to 12 years) groups showed lower levels. A similar decline was also observed in the mRNA of the AANAT enzyme and the expression levels of melatonin receptors. However, ASMT expression was exactly the opposite, with low levels in the newborn group and higher levels in the years group. Our results show that the thymic synthesis of melatonin occurs very early in childhood. Additionally, this is the first report that is focused on melatonin receptors expression in the human thymus. Considering the limited melatonin synthesis performed by the newborn pineal gland, we suggest that the high levels of melatonin found in human thymus in this experimental group arise from synthesis in the tissue itself, which could be contributing to the immune efficiency at the thymic level. • Melatonin biosynthetic machinery in the human thymus from children changes with age. • Melatonin content in the human thymus is higher in newborns. • The thymus not only synthesizes melatonin but also responds to it. • The melatonin effector system decreases throughout childhood. [ABSTRACT FROM AUTHOR]

Melatonin affects diverse physiological functions through its receptor and plays an important role in the central nervous system. In the present study, we compared immunoreactivity patterns of arylalkylamine N-acetyltransferase (AANAT), an enzyme essential for melatonin synthesis, and melatonin receptor type 1B (MT2) in the spinal cord of young adult (2~3 years) and aged (10~ 12 years) beagle dogs using immunohistochemistry and Western blotting. AANAT-specific immunoreactivity was observed in the nuclei of spinal neurons, and was significantly increased in aged dog spinal neurons compared to young adult spinal neurons. MT2-specific immunoreactivity was found in the cytoplasm of spinal neurons, and was predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs. These increased levels of AANAT and MT2 immunoreactivity in aged spinal cord might be a feature of normal aging and associated with a feedback mechanism that compensates for decreased production of melatonin during aging. [ABSTRACT FROM AUTHOR]

Abstract: A melatonin receptor is a G protein-coupled receptor (GPCR) which binds melatonin. Three types of melatonin receptor have been cloned. The MT1 (or Mel1A or MTNR1A) and MT2 (or Mel1B or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 (or Mel1C or MTNR1C) has been identified in amphibia and birds. The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the research progress on melatonin receptor in poultry. [Copyright &y& Elsevier]

The article reports on the cloning of the melatonin receptor subtype MT1 of ewe.

Melatonin, an important neuromodulator involved in circadian rhythms, modulates a series of physiological processes via activating its specific receptors, namely Mel1a (MT 1), Mel1b (MT 2) and Mel1c receptors. In this work, the localization of Mel1b receptor was studied in pigeon retina using double immunohistochemistry staining and confocal scanning microscopy. Our results showed that Mel1b receptor widely existed in the outer segment of photoreceptors and in the somata of dopaminergic amacrine cells, cholinergic amacrine cells, glycinergic AII amacrine cells, conventional ganglion cells and intrinsically photosensitive retinal ganglion cells, while horizontal cells, bipolar cells and Müller glial cells seemed to lack immunoreactivity of Mel1b receptor. That multiple types of retinal cells expressing Mel1b receptor suggests melatonin may directly modulate the activities of retina via activating Mel1b receptor. • Mel1b exists in photoreceptors, dopaminergic ACs, cholinergic ACs, glycinergic AII ACs, RGCs and ipRGCs. • HCs, BCs and Müller glial cells seems to lack immunoreactivity of Mel1b receptor in pigeon retina. • Researches on circadian rhythm-related Mel1b in the retina of pigeon contributes to studies of the biological rhythm. [ABSTRACT FROM AUTHOR]