Expression of melatoninergic receptors in human placental choriocarcinoma cell lines

doi:10.1093/HUMREP/DEL120

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Expression of melatoninergic receptors in human placental choriocarcinoma cell lines

Journal Article•DOI•

Expression of melatoninergic receptors in human placental choriocarcinoma cell lines

Dave Lanoix¹, Rodney J. Ouellette, Cathy Vaillancourt¹, Cathy Vaillancourt²•Institutions (2)

Université de Moncton¹, Université du Québec à Montréal²

01 Aug 2006-Human Reproduction (Oxford University Press)-Vol. 21, Iss: 8, pp 1981-1989

TL;DR: These results demonstrate, for the first time, the expression of melatonin receptors in human term placental tissues and in choriocarcinoma cells and suggest a possible paracrine/autocrine function for melatonin in human placenta.

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Abstract: Lanoix D, Ouellette R, Vaillancourt C. Melatonin crosses the placenta and enters the fetal circulation. Moreover, experimental data suggest a possible influence of melatonin on placental function and fetal development in humans. To date, the expression and role of melatonin receptors in human placenta choriocarcinoma cell lines and in human term placental tissues remain to be elucidated. METHODS AND RESULTS : Results from RT-PCR, western blotting and confocal microscopy demonstrated that the (...)

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Journal Article•DOI•

Extrapineal melatonin: sources, regulation, and potential functions.

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Darío Acuña-Castroviejo¹, Germaine Escames¹, Carmen Venegas¹, María E. Díaz-Casado¹, Elena Lima-Cabello¹, Luis C. López¹, Sergio Rosales-Corral², Dun Xian Tan², Russel J. Reiter² - Show less +5 more•Institutions (2)

University of Granada¹, University of Texas Health Science Center at San Antonio²

20 Feb 2014-Cellular and Molecular Life Sciences

TL;DR: The presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans is emphasized and information related to its peripheral production and regulation of this ubiquitously acting indoleamine is compiled.

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Abstract: Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.

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757 citations

Cites result from "Expression of melatoninergic recept..."

...However, other authors have published contrary results [268], although it involved a different experimental model (normal first-trimester trophoblasts cells vs....
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Journal Article•DOI•

Melatonin—A pleiotropic, orchestrating regulator molecule

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Rüdiger Hardeland¹, Daniel P. Cardinali², Venkatramanujam Srinivasan³, D. Warren Spence, Gregory M. Brown⁴, Seithikurippu R. Pandi-Perumal - Show less +2 more•Institutions (4)

University of Göttingen¹, Facultad de Ciencias Médicas², Karpagam University³, Centre for Addiction and Mental Health⁴

01 Mar 2011-Progress in Neurobiology

TL;DR: Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging.

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709 citations

Cites background from "Expression of melatoninergic recept..."

...Additional information exists on the expression of MT1 and MT2 in various human cancer cell lines of different origin (Xi et al., 2000; Dillon et al., 2002; Ekmekcioglu, 2006; Lanoix et al., 2006; Aust et al., 2008; Nakamura et al., 2008; Carbajo-Pescador et al., 2009)....
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...…2003, 2004), breast epithelium (Dillon et al., 2002), myometrium (MT1, MT2, Schlabritz-Loutsevitch et al., 2003; Sharkey et al., 2010), placenta (MT1, MT2, Lanoix et al., 2006), granulosa and luteal cells (MT1, MT2, Yie et al., 1995; Niles et al., 1999; Woo et al., 2001; Tamura et al., 2009),…...
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Journal Article•DOI•

Melatonin membrane receptors in peripheral tissues: distribution and functions.

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Radomir M. Slominski¹, Russel J. Reiter², Natalia Schlabritz-Loutsevitch¹, Rennolds S. Ostrom¹, Andrzej Slominski¹ - Show less +1 more•Institutions (2)

University of Tennessee Health Science Center¹, University of Texas Health Science Center at San Antonio²

04 Apr 2012-Molecular and Cellular Endocrinology

TL;DR: Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes.

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538 citations

Cites methods from "Expression of melatoninergic recept..."

...All three receptors were detected using RT-PCR, Western blotting and confocal microscopy in the human term placental tissues and in choriocarcinoma cell lines JEG-3 and BeWo (Lanoix et al., 2006)....
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Journal Article•DOI•

Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology

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Russel J. Reiter¹, Dun Xian Tan¹, Ahmet Korkmaz, Sergio Rosales-Corral•Institutions (1)

University of Texas Health Science Center at San Antonio¹

01 Mar 2014-Human Reproduction Update

TL;DR: Melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis and a number of conclusions naturally evolve from the data summarized in this review.

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Abstract: Background Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review Methods Databases were searched for the related published English literature up to 15 May 2013 The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals The results of the studies uncovered are summarized herein Results Both melatonin and circadian rhythms impact reproduction, especially during pregnancy Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction This may contribute to pre-eclampsia and other disorders which often complicate pregnancy Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy Finally, melatonin synergizes with oxytocin to promote delivery of the fetus Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions Conclusions A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin

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227 citations

Journal Article•DOI•

Melatonin receptors: molecular pharmacology and signalling in the context of system bias

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Erika Cecon¹, Erika Cecon², Erika Cecon³, Atsuro Oishi¹, Atsuro Oishi³, Atsuro Oishi², Ralf Jockers¹, Ralf Jockers², Ralf Jockers³ - Show less +5 more•Institutions (3)

Paris Descartes University¹, French Institute of Health and Medical Research², Centre national de la recherche scientifique³

01 Aug 2018-British Journal of Pharmacology

TL;DR: Bias at the level of the receptor, by the expression of genetic receptor variants, will be discussed to show how a modified receptor function can have an effect on the risk for common diseases like type 2 diabetes in humans.

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Abstract: Melatonin, N-acetyl-5-methoxytryptamine, an evolutionally old molecule, is produced by the pineal gland in vertebrates, and it binds with high affinity to melatonin receptors, which are members of the GPCR family. Among the multiple effects attributed to melatonin, we will focus here on those that are dependent on the activation of the two mammalian MT1 and MT2 melatonin receptors. We briefly summarize the latest developments on synthetic melatonin receptor ligands, including multi-target-directed ligands, and the characterization of signalling-biased ligands. We discuss signalling pathways activated by melatonin receptors that appear to be highly cell- and tissue-dependent, emphasizing the impact of system bias on the functional outcome. Different proteins have been demonstrated to interact with melatonin receptors, and thus, we postulate that part of this system bias has its molecular basis in differences of the expression of receptor-associated proteins including heterodimerization partners. Finally, bias at the level of the receptor, by the expression of genetic receptor variants, will be discussed to show how a modified receptor function can have an effect on the risk for common diseases like type 2 diabetes in humans. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.

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144 citations

Cites methods from "Expression of melatoninergic recept..."

...…kidney RT-PCR Drew et al. (1998) Granulosa cells RT-PCR Soares et al. (2003) Niles et al. (1999) Placental tissues RT-PCR and Western blot Lanoix et al. (2006) Myometrium In-situ hybridization Schlabritz-Loutsevitch et al. (2003) RT-PCR Sharkey et al. (2009) Pancreatic alpha and beta…...
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Journal Article•DOI•

DNA sequencing with chain-terminating inhibitors

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Frederick Sanger, S Nicklen, Alan Coulson

01 Dec 1977-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: A new method for determining nucleotide sequences in DNA is described, which makes use of the 2',3'-dideoxy and arabinon nucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase.

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Abstract: A new method for determining nucleotide sequences in DNA is described. It is similar to the “plus and minus” method [Sanger, F. & Coulson, A. R. (1975) J. Mol. Biol. 94, 441-448] but makes use of the 2′,3′-dideoxy and arabinonucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase. The technique has been applied to the DNA of bacteriophage ϕX174 and is more rapid and more accurate than either the plus or the minus method.

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62,728 citations

"Expression of melatoninergic recept..." refers methods in this paper

...Nucleotide sequences for MT1 and MT2 melatonin receptors were analysed by the dideoxynucleotide chain termination method of Sanger et al. (1977) using ThermoSequenase (Amersham Biosciences, Piscataway, NJ, USA)....
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Journal Article•DOI•

Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses

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Steven M. Reppert¹, David R. Weaver¹, Takashi Ebisawa¹•Institutions (1)

Harvard University¹

01 Nov 1994-Neuron

TL;DR: The cloning and characterization of a high affinity receptor for melatonin from the sheep and human is reported, likely mediates the reproductive and circadian actions of melatonin in mammals.

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1,089 citations

"Expression of melatoninergic recept..." refers background in this paper

...Human MT1 (Mel1a, ML1A or mt1) and MT2 (Mel1b or ML1B) melatonin receptors have been cloned, and both are members of the G-protein-coupled receptor (GPCR) superfamily (Reppert et al., 1994, 1995)....
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...…most MT1 and MT2 receptors are generally expressed in brain and retina, respectively, they are also widely distributed in a variety of other tissues, including ovarian follicles, prostate, cells of the immune system and kidney (Reppert et al., 1994, 1995; Naji et al., 2004; Pozo et al., 2004)....
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Journal Article•DOI•

Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor

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Steven M. Reppert¹, Catherine Godson, Cathy D. Mahle, David R. Weaver, Susan A. Slaugenhaupt, James F. Gusella - Show less +2 more•Institutions (1)

Harvard University¹

12 Sep 1995-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: The Mel1b melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects ofmelatonin in mammals.

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Abstract: A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel1a melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel1b melatonin receptor. The Mel1b receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel1a receptor. Transient expression of the Mel1b receptor in COS-1 cells results in high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel1a melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel1b melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel1b melatonin receptor is expressed in retina and, to a lesser extent, brain. PCR analysis of human-rodent somatic cell hybrids maps the Mel1b receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel1b melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals.

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862 citations

"Expression of melatoninergic recept..." refers background in this paper

...Moreover, the cloned MT2 receptor (Reppert et al., 1995) has a predicted molecular weight of 40 kDa, not including post-translational modifications, which is similar to that reported for the deglycosylated receptor (38 kDa) (Prada et al., 2005), suggesting that the bands we observed at 36 and 40…...
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...Human MT1 (Mel1a, ML1A or mt1) and MT2 (Mel1b or ML1B) melatonin receptors have been cloned, and both are members of the G-protein-coupled receptor (GPCR) superfamily (Reppert et al., 1994, 1995)....
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...Moreover, the cloned MT2 receptor (Reppert et al., 1995) has a predicted molecular weight of 40 kDa, not including post-translational modifications, which is similar to that reported for the deglycosylated receptor (38 kDa) (Prada et al....
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...…most MT1 and MT2 receptors are generally expressed in brain and retina, respectively, they are also widely distributed in a variety of other tissues, including ovarian follicles, prostate, cells of the immune system and kidney (Reppert et al., 1994, 1995; Naji et al., 2004; Pozo et al., 2004)....
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Journal Article•DOI•

Orphan nuclear receptors: from gene to function.

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Vincent Giguère¹•Institutions (1)

McGill University Health Centre¹

01 Oct 1999-Endocrine Reviews

TL;DR: I. Nuclear Receptors: General Concepts and Orphans in Search of a Home.

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Abstract: I. Introduction II. Nuclear Receptors: General Concepts A. Anatomy of nuclear receptors B. Mechanisms of action III. Orphan Nuclear Receptors A. Definition B. Nomenclature C. Structural and functional diversity IV. Novel Hormone Response Systems: RXR and Its Heterodimeric Partners A. RXR: rexinoids B. PPAR: multiple ligands, multiple functions C. PXR: pregnanes, xenobiotic compounds, and benzoate derivatives D. CAR (constitutive androstane receptor): androstanes and phenobarbital E. LXR: control of cholesterol metabolism by oxysterols F. FXR: bile acids receptor V. Orphans in Search of a Home A. HNF4: diabetes and possible regulation by acyl-coenzyme A (CoA) thioesters B. FTZ-F1: steroidogenesis and sexual development C. Rev-Erb: singular members of the superfamily D. ROR: neuron development and T cell selection E. TR2: the testis receptors F. TLX: forebrain development G. COUP-TF: neurogenesis, angiogenesis, and heart development H. ERR: placenta development and control of lipid metabolism I. NGFI-B: hyp...

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861 citations

"Expression of melatoninergic recept..." refers background in this paper

...Some researchers have questioned the validity of the melatonin-binding studies to ROR/RZR receptors and further suggest that these receptors may not be the correct or the only nuclear receptors for melatonin (Giguere, 1999)....
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Journal Article•DOI•

Functional MT1 and MT2 melatonin receptors in mammals.

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Margarita L. Dubocovich¹, Magdalena Markowska¹•Institutions (1)

Northwestern University¹

01 Jul 2005-Endocrine

TL;DR: The melatonin-mediated responses elicited by activation of MT1 and MT2 native melatonin receptors are dependent on circadian time, duration and mode of exposure to endogenous or exogenous melatonin, and functional receptor sensitivity.

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Abstract: Melatonin, dubbed the hormone of darkness, is known to regulate a wide variety of physiological processes in mammals. This review describes well-defined functional responses mediated through activation of high-affinity MT1 and MT2 proteinteoupled receptors viewed as potential targets for drug discovery. MT1 melatonin receptors modulate neuronal firing, arterial vasoconstriction, cell proliferation in cancer cells, and reproductive and metabolic functions. Ativation of MT2 melatonin receptors phase shift circadian rhythms of neuronal firing in the suprachiasmatic nucleus, inhibit dopamine release in retina, induce vasodilation and inhibition of leukocyte rolling in arterial beds, and enhance immune responses. The melatonin-mediated responses elicited by activation of MT1 and MT2 native melatonin receptors are dependent on circadian time, duration and mode of exposure to endogenous or exogenous melatonin, and functional receptor sensitivity. Together, these studies underscore the importance of carefully linking each melatonin receptor type to specific functional responses in target tissues to facilitate the design and development of novel therapeutic agent.

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776 citations

"Expression of melatoninergic recept..." refers background in this paper

...2 toxin (PTX)-sensitive G protein, a process known to be mediated by Gi/o proteins, resulting in decreases in protein kinase A activity and in cAMP-response element-binding protein phosphorylation (for review, see Witt-Enderby et al., 2003; Dubocovich and Markowska, 2005)....
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...…D ow nloaded from toxin (PTX)-sensitive G protein, a process known to be mediated by Gi/o proteins, resulting in decreases in protein kinase A activity and in cAMP-response element-binding protein phosphorylation (for review, see Witt-Enderby et al., 2003; Dubocovich and Markowska, 2005)....
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...Several studies in various tissues demonstrated that melatonin can inhibit cAMP secretion via PTX-sensitive G proteins (Gi/o) coupled to MT1 and MT2 receptors (reviewed in Dubocovich and Markowska, 2005; Witt-Enderby et al., 2003)....
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