メラトニン受容体、メラトニンレセプター

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
hormone secreted by the pineal gland

PrepTutorEJDIC

=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/01 15:14:38」(JST)

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A melatonin receptor is a G protein-coupled receptor (GPCR) which binds melatonin.^[1]

Three types of melatonin receptor have been cloned. The MT₁ (or Mel_1A or MTNR1A) and MT₂ (or Mel_1B or MTNR1B) receptor subtypes are present in humans and other mammals,^[2] while an additional melatonin receptor subtype MT₃ (or Mel_1C or MTNR1C) has been identified in amphibia and birds.^[3]

Expression patterns

In mammals, melatonin receptors are found in the brain and some peripheral organs. However, there is considerable variation in the density and location of MT receptor expression between species.^[4]

MT₁

In humans, The MT₁ subtype is expressed in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus.

MT₂

The MT₂ subtype is expressed in the retina. MT₂ receptor mRNA has not been detected by in situ hybridization in the rat suprachiasmatic nucleo or pars tubealis.^[5]

MT₃

The MT₃ subtype of many non-mammalian vertebrates is expressed in various brain areas.^[3]

MT Receptor function

MT₁

In humans, The MT₁ subtype's expression in the pars tuberalis of the pituitary gland and suprachiamatic nuclei of the hypothalamus is indicative of melatonin's circadian and reproductive functional involvement.

MT₂

In humans, the MT₂ subtype's expression in the retina is suggestive of melatonin's effect on the mammalian retina occurring through this receptor. Research suggests that melatonin acts to inhibit the Ca2+-dependent release of dopamine.^[5] Melatonin's action in the retina is believed to affect several light-dependent functions, including phagocytosis and photopigment disc shedding.^[6]

MT₃

Selective Ligands

Agonists

Agomelatine
LY-156,735^[7]
Melatonin
Piromelatine
Ramelteon
Tasimelteon

Antagonists

Afobazole
Luzindole

References

^ Reppert SM (1997). "Melatonin receptors: molecular biology of a new family of G protein-coupled receptors". J. Biol. Rhythms 12 (6): 528–31. doi:10.1177/074873049701200606. PMID 9406026.
^ Reppert SM, Weaver DR, Godson C (1996). "Melatonin receptors step into the light: cloning and classification of subtypes". Trends Pharmacol. Sci. 17 (3): 100–2. doi:10.1016/0165-6147(96)10005-5. PMID 8936344.
^ ^a ^b Sugden D, Davidson K, Hough KA, Teh MT (2004). "Melatonin, melatonin receptors and melanophores: a moving story". Pigment Cell Res. 17 (5): 454–60. doi:10.1111/j.1600-0749.2004.00185.x. PMID 15357831.
^ Morgan PJ, Barrett P, Howell HE, Helliwell R (1994). "Melatonin receptors: localization, molecular pharmacology and physiological significance". Neurochem. Int. 24 (2): 101–46. doi:10.1016/0197-0186(94)90100-7. PMID 8161940.
^ ^a ^b Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. Bibcode:1995PNAS...92.8734R. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
^ Besharse JC, Dunis DA (March 1983). "Methoxyindoles and photoreceptor metabolism: activation of rod shedding". Science 219 (4590): 1341–3. Bibcode:1983Sci...219.1341B. doi:10.1126/science.6828862. PMID 6828862.
^ Nickelsen T, Samel A, Vejvoda M, Wenzel J, Smith B, Gerzer R (September 2002). "Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9h time shift: results of a placebo-controlled trial". Chronobiol. Int. 19 (5): 915–36. doi:10.1081/cbi-120014108. PMID 12405554.

External links

"Melatonin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Melatonin Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

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UpToDate Contents

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1. メラトニンの生理学および臨床使用 physiology and clinical use of melatonin
2. 緩和ケアにおける不眠症の概要 overview of insomnia in palliative care
3. 睡眠の質および睡眠の構造に対する薬剤の効果 the effects of medications on sleep quality and sleep architecture
4. 時差ぼけ jet lag
5. 不眠症の治療 treatment of insomnia

English Journal

Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter release.

Choi TY1, Kwon JE1, Durrance ES1, Jo SH2, Choi SY3, Kim KT4.Author information 1Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.2Department of Physiology, Institute of Bioscience and Biotechnology, BK21 Plus Graduate Program, Kangwon National University College of Medicine, Chuncheon 200-701, Republic of Korea.3Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea; Department of Life Sciences, Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: sychoi@snu.ac.kr.4Department of Life Sciences, Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: ktk@postech.ac.kr.AbstractMelatonin is involved in various neuronal functions such as circadian rhythmicity and thermoregulation. Melatonin has a wide range of pharmacologically effective concentration levels from the nanomolar to millimolar levels. Recently, the antiepileptic effect of high dose melatonin has been the focus of clinical studies; however, its detailed mechanism especially in relation to neurotransmitter release and synaptic transmission remains unclear. We studied the effect of melatonin at high concentrations on the neurotransmitter release by monitoring norepinephrine release in PC12 cells, and excitatory postsynaptic potential in rat hippocampal slices. Melatonin inhibits the 70mM K(+)-induced Ca(2+) increase at millimolar levels without effect on bradykinin-triggered Ca(2+) increase in PC12 cells. Melatonin (1mM) did not affect A2A adenosine receptor-evoked cAMP production, and classical melatonin receptor antagonists did not reverse the melatonin-induced inhibitory effect, suggesting G-protein coupled receptor independency. Melatonin inhibits the 70mM K(+)-induced norepinephrine release at a similar effective concentration range in PC12 cells. We confirmed that melatonin (100µM) inhibits excitatory synaptic transmission of the hippocampal Schaffer collateral pathway with the decrease in basal synaptic transmission and the increase in paired pulse ratio. These results show that melatonin inhibits neurotransmitter release through the blocking of voltage-sensitive Ca(2+) channels and suggest a possible mechanism for the antiepileptic effect of melatonin.
Brain research.Brain Res.2014 Apr 4;1557:34-42. doi: 10.1016/j.brainres.2014.02.023. Epub 2014 Feb 18.
Melatonin is involved in various neuronal functions such as circadian rhythmicity and thermoregulation. Melatonin has a wide range of pharmacologically effective concentration levels from the nanomolar to millimolar levels. Recently, the antiepileptic effect of high dose melatonin has been the focus
PMID 24560601

Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms.

Castanho A1, Bothorel B, Seguin L, Mocaër E, Pévet P.Author information 1Département de Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Intégratives, UPR 3212 CNRS, Université de Strasbourg , Strasbourg , France and.AbstractDepression and biological rhythms disturbances are strongly associated. Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to modulate circadian rhythmicity controlled by the endogenous clock located in the suprachiasmatic nuclei (SCN). The aim of the present study was to compare the effect of an acute injection of agomelatine (Ago), melatonin (MLT) or an antagonist 5-HT2c (S32006), on the rhythms of two robust clock outputs: the pineal MLT secretion and the body temperature rhythm (Tc). Daily endogenous MLT profiles were measured using transpineal microdialysis over 4 consecutive days in rats maintained on a 12 h light/12 h dark cycle. Simultaneously, Tc was recorded. The drugs were injected subcutaneously at three doses (1, 2.5 or 5 mg/kg) at the onset of darkness. Both Ago and MLT, at the dose of 2.5 mg/kg, increased the amplitude of the peak of MLT secretion and this effect was observed 2 d after injection. Moreover, both drugs induced a dose-dependent advance of the rhythm onset which resulted in lengthening of the MLT peak. S32006 had no effect on the rhythm of MLT. Ago, MLT and S32006 increased the amplitude of the rhythm of Tc. These data suggest a central action of Ago, directly on the SCN, via melatoninergic receptors responsible for both the increased amplitude of MLT rhythm and the phase advance. The increase in the amplitude of the body temperature could involve both MLT agonist and/or 5-HT2c antagonist properties of Ago.
Chronobiology international.Chronobiol Int.2014 Apr;31(3):371-81. doi: 10.3109/07420528.2013.860457. Epub 2013 Dec 11.
Depression and biological rhythms disturbances are strongly associated. Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to modulate circadian rhythmicity controlled by the endogenous clock located
PMID 24328729

2-Arachidonoyl glycerol sensitizes the pars distalis and enhances forskolin-stimulated prolactin secretion in Syrian hamsters.

Yasuo S1, Fischer C, Bojunga J, Iigo M, Korf HW.Author information 1Dr. Senckenbergische Anatomie, Institut für Anatomie II and.Abstract2-Arachidonoyl glycerol (2-AG) is a major endocannabinoid and an important regulator of neuroendocrine system. In Syrian hamster and human, we found that 2-AG is synthesized in the hypophysial pars tuberalis (PT), an interface between photoperiodic melatonin signals and neuroendocrine output pathways. The target of 2-AG produced in the PT is likely to be the pars distalis (PD). Here we demonstrate that 2-AG in combination with forskolin stimulated prolactin secretion from PD organ cultures of Syrian hamsters, whereas incubation with 2-AG alone had no effect. Forskolin-induced prolactin secretion was also significantly enhanced when cultured PD tissue was preincubated with 2-AG. The stimulatory effects of 2-AG on prolactin secretion were blocked by AM251, a selective CB1 antagonist, and were still observed in the presence of quinpirole, a D2-class dopamine receptor agonist. 2-AG also enhanced prolactin secretion in the presence of adenosine, while it had little effect when applied together with adenosine diphosphate (ADP) and adenosine triphosphate (ATP). Moreover, the effect of forskolin was mimicked by adenosine in a dose-dependent manner. In conclusion, our data suggest that 2-AG sensitizes the PD tissue to potentiate the stimulating effects of forskolin and adenosine on prolactin secretion and thus provide novel insight into the mode of action of 2-AG in the PD.
Chronobiology international.Chronobiol Int.2014 Apr;31(3):337-42. doi: 10.3109/07420528.2013.852104. Epub 2013 Nov 7.
2-Arachidonoyl glycerol (2-AG) is a major endocannabinoid and an important regulator of neuroendocrine system. In Syrian hamster and human, we found that 2-AG is synthesized in the hypophysial pars tuberalis (PT), an interface between photoperiodic melatonin signals and neuroendocrine output pathway
PMID 24200164

Japanese Journal

Efficient Synthesis of [11C]Ramelteon as a Positron Emission Tomography Probe for Imaging Melatonin Receptors Involved in Circadian Rhythms

Takashima-Hirano Misato,Tazawa Syusaku,Takahashi Kazuhiro,Doi Hisashi,Suzuki Masaaki
CHEMICAL & PHARMACEUTICAL BULLETIN 59(8), 1062-1064, 2011
… Ramelteon (TAK-375) is a novel melatonin receptor agonist that is used for clinical treatment of insomnia. … [11C]Ramelteon is a potential positron emission tomography (PET) probe for imaging the melatonin receptor. …
NAID 130000960943

メラトニン受容体作動薬ラメルテオン(ロゼレム^【○!R】錠8mg)の薬理作用と臨床試験成績

平井圭介,加藤浩紀,西川久夫,行弘信仁,西山啓次,宮本政臣
日本薬理学雑誌 136(1), 51-60, 2010-07-01
既存の睡眠薬は，GABAA受容体に作用して睡眠を誘発する．GABAA受容体は，脳幹毛様体，辺縁系，海馬，小脳，脊髄，大脳皮質辺縁系など広範囲に存在し，種々の神経伝達物質を含有する神経に対して， Cl−イオンの細胞内流入を介して抑制的に作用する．そのため，睡眠誘発作用は示すものの，その睡眠は自然睡眠とは異なり，筋弛緩作用，前向性健忘，反跳性不眠，依存性などの種々の有害作用を惹起する．これに対してラメ …
NAID 10026544589