• 동의신경정신과학회지
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• 제18권1호
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• pp.15-36
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• 2007

Objective : This study was to investigate the effects of several herbs on the levels of MT1 and MT2 melatonin receptors Methods: It was investigated the effects of several herbs such as WEDL, WEZV, WEFO, WEOC on the levels of MT1 and MT2 melatonin receptors using C6 glial cell model. ${\beta}-estradiol$ treatment, as a positive control group, under non-cytotoxic condition. Results : 1. The water extracts of Dimocarpus long (WEDL) induced the levels of MT2 melatonin receptor expression in a concentration-dependent manner without altering the levels of MT1 melatonin receptor expression. 2. The treatment with the water extract of Zizyphus vulgaris (WEZV) induced the levels of MT1 melatonin receptor expression and the levels of MT2 melatonin receptor expression was not affected. 3. The levels of MT1 as well as MT2 melatonin receptor expression were markedly up-regulated in the water extract of Fossilia ossis (WEFO) and the water extract of Ostreae caro (WEOC)-treated C6 cells. 4. The combination treatment with WEDL and WEZV induced not only the levels of MT1 melatonin receptor expression but also MT2 melatonin receptor expression, but the synergic effects of the combination treatment with WEFO and WEOC were not detected in C6 cells. Conclusion : The study provides important new insights into the possible mechanisms on the regulation of melatonin receptor synthesis by WEDL, WEZV, WEFO and WEOC.

• 한국발생생물학회지:발생과생식
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• 제6권1호
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• pp.45-54
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• 2002

골든 햄스터의 생식활동은 광주기에 의해 조절된다. 그들의 생식능력은 여름에 왕성하고 겨울에는 퇴화한다. 송과선에서 분비되는 멜라토닌은 계절적 번식동물에서 생식활동을 중재한다. 멜라토닌 수용체가 최근에 사람을 포함하는 몇몇 동물에서 확인되었지만 골든 햄스터의 생식능력과 관련하여 알려진 바가 많지 않다. 역전사 PCR 방법을 사용하여 멜라토닌 수용체의 일부 유전자를 동정하였다(309 염기). 멜라토닌 수용체의 핵산 서열과 추론된 아미노산 서열을 보고된 다른 동물들과 비교하였다. 멜라토닌 수용체는 시상하부, 뇌하수체, 혈액, 지라에서 명백히 탐지되었다. 광주기가 정소 무게 및 생식 호르몬에 현저한 영향을 주었지만 멜라토닌 수용체의 발현에는 영향을 뚜렷하게 보이지 않았다. 이러한 결과는 생식을 조절하는 멜라토닌은 그 수용체의 수보다 수용체에 결합하는 친화도가 더 중요함을 시사한다.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.35-43
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• 1999

Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melationin is also neuroportective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu, Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal monogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

• 동의신경정신과학회지
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• 제21권2호
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• pp.103-123
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• 2010

Objectives : This study was to investigate the effect of several herbal prescriptions such as Tianwangbuxindan qu zhusha, Tianwangbuxindan, Wendantang, Guipitang on the level of $MT_1$ and $MT_2$ melatonin receptors in C6 glial cells. Methods : For this study, we exposed of C6 cells to several herbal prescriptions resulted in non-cytotoxic in various dose as measured by MTT assay, trypan blue count, morphology change and DAPI stain. Results : Tianwangbuxindan qu zhush and Tianwangbuxindan induced the levels of $MT_1$ melatonin receptor expression in a dose-dependent manner without altering the level of $MT_2$ melatonin receptor expression. However, the treatment with Wendantang, Guipitang don't effect of $MT_1$ and $MT_2$ melatonin receptor expression. Conclusions : This results suggest that Tianwangbuxindan can be a promising the regulation of melatonin receptor synthesis, and further studies will be needed to clarify the mechanism.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.37-41
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• 2008

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

• 한국발생생물학회지:발생과생식
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• 제17권1호
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• pp.45-53
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• 2013

The action of melatonin within the body of animals is known to be mediated by melatonin receptors. Three different types of melatonin receptors have been identified so far in fish. However, which of these are specifically involved in puberty onset is not known in fish. We cloned and analyzed the sequence of melatonin receptor 1a (mel 1a) gene in Nile tilapia Oreochromis niloticus. In addition, we examined the tissue distribution of gene expressions for three types of receptors, mel 1a, 1b and lc and investigated which of them is involved in the onset of puberty by comparing their expression with that of gonadotropin-releasing hormone receptor I (GnRHr I) gene using quantitative real-time PCR from 1 week post hatch (wph) to 24 wph. The mel 1a gene of Nile tilapia consisted of two exons and one bulky intron between them. Mel 1a gene was found to be highly conserved gene showing high homology with the corresponding genes from different teleost. All three types of melatonin receptor genes were expressed in the brain, eyes and ovary in common. Expression of mel 1a gene was the most abundant and ubiquitous among 3 receptors in the brain, liver, gill, ovary, muscle, eye, heart, intestine, spleen and kidney. Mel 1b and mel 1c genes were, however, expressed in fewer tissues at low level. During the development post hatch, expressions of both mel 1a and GnRHr I genes significantly increased at 13 wph which was close to the putative timing of puberty onset in this species. These results suggest that among three types of receptors mel 1a is most likely associated with the action of melatonin in the onset of puberty in Nile tilapia.

• 대한수의학회지
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• 제41권4호
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• pp.497-503
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• 2001

Evidence from the last 10 years have been suggested that melatonin mainly produce a depressant effect on the cardiac system, but we found an activating effect of melatonin on heart rate in this research. To determine the hypothesis that melatonin has dual effects on physiological behaviour of cardiac system, we investigated the effects of melatonin on heart rate in isolated rat atria and anesthetized rats. Regardless of concentration, melatonin produced bradycardia in the 84 cases of 148 experiments (57 %) and tachycardia in the 64 cases of 148 experiments (43 %). And in atrium, melatonin produced a decrease automaticity in 52 cases of 86 experiments (60 %) and increase automaticity in 40 % (34/86 cases). Also, these effects are not significnat relationship with concetration of melatonin. The melatonin-induced bradycardia in vivo was inhibited by pretreatment of atropine or bilateral cervical vagotomy. Also, in isolated atrium the melatonin-induced decrease in automaticity was inhibited by pretreatment of atropine. These melatonin-induced responses were potenitated by pretreatment of propranolol. The melatonin-induced tachycardia in vivo was inhibited by pretreatment of propranolol, nifedipine or bilateral cervical vagotomy, but not by pretreatment of atropine. The melatonin-induced incease in automaticity in isolated atrium was converted to decrease in automaticity by pretreatment of propranolol. In addition, the change in heart rate caused by adrenoceptor agonists was inhibited by pretreatment of melatonin. These results indicate that melatonin-induced bradycardia may be related to a muscarinic receptor activation and melatonin-induced tachycardia may be related to a $\beta$-adrenoceptor stimulation.

• 한국산학기술학회논문지
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• 제6권2호
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• pp.183-188
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• 2005

포유동물에서는 두가지의 receptor가 보고되었다. 각 sample을 RNA extraction, RT-PCR, Realtime-PCR을 실시하여 melatonin 1A, 1B의 발현 양을 분석하였다. MT1A는 cerebellum에서는 3 hours에서 약 1/8배로 감소를 보이고 6 hours에서는 정상치 9 hours에서는 16배정도로 많은 양의 증가율 보였다. 나머지 hippocampus, thalamus, hypothalamus에서는 공통적으로 3 hours에서 많게는 10배에서, 적게는 대조군과 거의 비슷한 1.5배정도의 증가율을 보이고 있으며, 6 hours에서는 모두 감소하는 것을 알 수 있다. MT1B에서는 4 group 모두 3 hours, 6 hours에서 receptor의 양이 확연히 줄어들었다. 9 hours의 경우에는 4 group모두에서 적게는 8배, 많게는 거의 1000배 가까이의 발현 양의 차이가 나타났다.

• Journal of Veterinary Science
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• 제22권4호
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• pp.54.1-54.13
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• 2021

Background: Hypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase. Objectives: This study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation. Methods: Mouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated. Results: Under hypoxic condition, the mRNA expression of cardiac-lineage markers (Brachyury, Tbx20, and cTn1) and melatonin receptor (Mtnr1a) was reduced. The mRNA expression of cTn1 and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and Mtnr1a mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects. Conclusions: This study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.

• 한국발생생물학회지:발생과생식
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• 제12권2호
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• pp.125-132
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• 2008

멜라토닌(N-acetyl-5-methoxytryptamine)은 포유동물의 뇌의 송과선에서 분비되는 호르몬으로 수면과 생체 리듬 등을 조절하고 난소 기능과 번식에도 영향을 미친다. 또한, 강력한 scavenger로서 항산화제의 역할을 한다. 이 연구의 목적은 멜라토닌이 생쥐 난구세포-핵낭(germinal vesicle, GV) 시기 난자 복합체의 체외성숙에 미치는 영향을 알아보는 것이다. 3주령의 ICR 암컷 생쥐의 난소에서 회수된 난자-난구세포 복합체를 0, 0.1 nM, 10 nM, 1,000 nM의 멜라토닌이 첨가된 배양액에서 18시간 동안 배양하고, 제1극체의 방출 여부를 확인하여 성숙율을 확인하였다. 체외성숙 후 TUNEL assay와 성숙율이 가장 높게 나타났다. 체외성숙된 난자에서는 세포자연사가 나타나지 않았으나 난구세포에서는 관찰되었으며, 1,000 nM을 첨가하여 배양한 군의 난구세포는 유의하게 낮은 세포자연사를 나타냈다. 그리고 1,000 nM의 멜라토닌을 첨가한 군의 난구세포에서 멜라토닌 수용체의 mRNA가 대조군에 비해 낮게 발현되었다. 이상의 결과를 종합하면 체외성숙 배양액에 첨가된 멜라토닌은 난구세포의 세포자연사를 줄여줌으로써 생쥐 미성숙 난자의 체외성숙을 향상시키는 역할을 하는 것으로 사료된다.