{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:27Z","timestamp":1787022087876,"version":"build-2736575974"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"institut de recherche servier","award":["32000432"],"award-info":[{"award-number":["32000432"]}]},{"name":"institut de recherche servier","award":["32000432"],"award-info":[{"award-number":["32000432"]}]},{"name":"institut de recherche servier","award":["32000432"],"award-info":[{"award-number":["32000432"]}]},{"name":"INRAE"},{"name":"INRAE"},{"name":"INRAE"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Melatonin (MLT) is a biological modulator of circadian and seasonal rhythms and reproduction. The photoperiodic information is detected by retinal photoreceptors and transmitted through nerve transmissions to the pineal gland, where MLT is synthesized and secreted at night into the blood. MLT interacts with two G protein-coupled receptors, MT\n                    <jats:sub>1<\/jats:sub>\n                    and MT\n                    <jats:sub>2<\/jats:sub>\n                    . The aim of our work was to provide evidence for the presence of MLT receptors in the ovine pineal gland and define their involvement on melatonin secretion. For the first time, we identified the expression of MLT receptors with the specific 2-[\n                    <jats:sup>125<\/jats:sup>\n                    I]-MLT agonistic radioligand in ovin pinealocytes. The values of Kd and Bmax are 2.24 \u00b1 1.1 nM and 20 \u00b1 6.8 fmol\/mg. MLT receptors are functional and inhibit cAMP production and activate ERK1\/2 through pertussis toxin-sensitive G\n                    <jats:sub>i\/o<\/jats:sub>\n                    proteins. The MLT receptor antagonist\/ inverse agonist luzindole increased cAMP production (189 \u00b1 30%) and MLT secretion (866 \u00b1 13%). The effect of luzindole on MLT secretion was additive with the effect of well-described activators of this pathway such as the \u03b2-adrenergic agonist isoproterenol and the \u03b1-adrenergic agonist phenylephrine. Co-incubation of all three compounds increased MLT secretion by 1236 \u00b1 199%. These results suggest that MLT receptors are involved in the negative regulation of the synthesis of its own ligand in pinealocytes. While adrenergic receptors promote MLT secretion, MLT receptors mitigate this effect to limit the quantity of MLT secreted by the pineal gland.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0255249","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T14:43:21Z","timestamp":1627569801000},"page":"e0255249","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Negative regulation of melatonin secretion by melatonin receptors in ovine pinealocytes"],"prefix":"10.1371","volume":"16","author":[{"given":"Julie","family":"L\u00e9pinay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Taragnat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Chesneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Jockers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Delagrange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6500-3208","authenticated-orcid":true,"given":"V\u00e9ronique","family":"Bozon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"issue":"1","key":"pone.0255249.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18388\/abp.2007_3264","article-title":"Melatonin 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Guesdon","year":"2013","journal-title":"Psychoneuroendocrinology"},{"issue":"1","key":"pone.0255249.ref004","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-pharmtox-010814-124742","article-title":"MT1 and MT2 melatonin receptors: a therapeutic perspective","volume":"56","author":"J Liu","year":"2016","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"6","key":"pone.0255249.ref005","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"Melatonin as a hormone: new physiological and clinical insights","volume":"39","author":"J Cipolla-Neto","year":"2018","journal-title":"Endocr Rev"},{"key":"pone.0255249.ref006","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.yfrne.2018.06.004","article-title":"Exogenous melatonin as a treatment for secondary sleep disorders: a systematic review and meta-analysis. \u200e","volume":"52","author":"T Li","year":"2019","journal-title":"Front Neuroendocrinol"},{"issue":"391","key":"pone.0255249.ref007","first-page":"1","article-title":"Melatonin: countering chaotic time cues.","volume":"10","author":"J Arendt","year":"2019","journal-title":"Front Endocrinol"},{"key":"pone.0255249.ref008","first-page":"1","article-title":"Physiological and pharmacological perspectives of melatonin","volume":"10","author":"S Saptadip","journal-title":"Arch Physiol Biochem"},{"issue":"16","key":"pone.0255249.ref009","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: sources, regulation, and potential functions","volume":"71","author":"D Acu\u00f1a-Castroviejo","year":"2014","journal-title":"Cell Mol Life Sci"},{"issue":"3","key":"pone.0255249.ref010","doi-asserted-by":"crossref","DOI":"10.3390\/molecules23030652","article-title":"Seasonal reproduction in vertebrates: melatonin synthesis, binding, and functionality using Tinbergen\u2019s four questions.","volume":"23","author":"D Vivid","year":"2018","journal-title":"Molecules"},{"issue":"249","key":"pone.0255249.ref011","first-page":"1","article-title":"Melatonin synthesis and function: evolutionary history in animals and plants.","volume":"10","author":"D Zhao","year":"2019","journal-title":"Front Endocrinol"},{"issue":"5","key":"pone.0255249.ref012","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/0896-6273(94)90055-8","article-title":"Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses","volume":"13","author":"SM Reppert","year":"1994","journal-title":"Neuron"},{"issue":"19","key":"pone.0255249.ref013","doi-asserted-by":"crossref","first-page":"8734","DOI":"10.1073\/pnas.92.19.8734","article-title":"Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor","volume":"92","author":"SM Reppert","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"pone.0255249.ref014","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1096\/fasebj.2.12.2842214","article-title":"Pharmacology and function of melatonin receptors","volume":"2","author":"ML Dubocovich","year":"1988","journal-title":"FASEB J"},{"issue":"1","key":"pone.0255249.ref015","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/bph.12457","article-title":"Melatonin MT1 and MT2 receptors display different molecular pharmacologies only in the G-protein coupled state","volume":"171","author":"C Legros","year":"2014","journal-title":"Br J Pharmacol"},{"issue":"3","key":"pone.0255249.ref016","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1124\/jpet.115.229989","article-title":"Alternative radioligands for investigating the molecular pharmacology of melatonin receptors","volume":"356","author":"C Legros","year":"2016","journal-title":"J Pharmacol Exp Ther"},{"issue":"40","key":"pone.0255249.ref017","doi-asserted-by":"crossref","first-page":"31311","DOI":"10.1074\/jbc.M005141200","article-title":"Identification of the melatonin binding site MT3 as the quinone reductase 2","volume":"275","author":"O Nosjean","year":"2000","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0255249.ref018","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1124\/jpet.118.253260","article-title":"Is there sufficient evidence that the melatonin binding site MT3 is quinone reductase 2","volume":"368","author":"JA Boutin","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"pone.0255249.ref019","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1124\/pr.110.002832","article-title":"International union of basic and clinical pharmacology. LXXV. nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.","volume":"62","author":"ML Dubocovich","year":"2010","journal-title":"Pharmacol Rev."},{"issue":"18","key":"pone.0255249.ref020","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1111\/bph.13536","article-title":"Update on melatonin receptors: IUPHAR Review 20: Melatonin receptors","volume":"173","author":"R Jockers","year":"2016","journal-title":"Br J Pharmacol"},{"issue":"16","key":"pone.0255249.ref021","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1111\/bph.13950","article-title":"Melatonin receptors: molecular pharmacology and signalling in the context of system bias: melatonin receptor system bias","volume":"175","author":"E Cecon","year":"2018","journal-title":"Br J Pharmacol"},{"issue":"1\u20113","key":"pone.0255249.ref022","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0304-3940(89)90665-4","article-title":"Melatonin binding sites in the sheep pars tuberalis","volume":"100","author":"MM De Reviers","year":"1989","journal-title":"Neurosci Lett"},{"issue":"1","key":"pone.0255249.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2826.1989.tb00068.x","article-title":"Melatonin receptors on ovine pars tuberalis: characterization and autoradiographicai localization","volume":"1","author":"PJ Morgan","year":"1989","journal-title":"J Neuroendocrinol"},{"issue":"3","key":"pone.0255249.ref024","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/BF00327285","article-title":"Ultrastructure of melatonin-responsive cells in the ovine pars tuberalis","volume":"263","author":"PJ Morgan","year":"1991","journal-title":"Cell Tissue Res"},{"issue":"5","key":"pone.0255249.ref025","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-2826.1992.tb00204.x","article-title":"Melatonin regulates the synthesis and secretion of several proteins by pars tuberalis cells of the ovine pituitary","volume":"4","author":"PJ Morgan","year":"1992","journal-title":"J Neuroendocrinol"},{"issue":"1","key":"pone.0255249.ref026","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0006-8993(93)90256-M","article-title":"Melatonin receptor density is regulated in rat pars tuberalis and suprachiasmatic nuclei by melatonin itself","volume":"602","author":"F Gauer","year":"1993","journal-title":"Brain Res"},{"issue":"5","key":"pone.0255249.ref027","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1365-2826.1994.tb00615.x","article-title":"Melatonin regulates the phosphorylation of CREB in ovine pars tuberalis","volume":"6","author":"S McNulty","year":"1994","journal-title":"J Neuroendocrinol"},{"issue":"8","key":"pone.0255249.ref028","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1365-2826.1996.tb00699.x","article-title":"Phosphorylation of CREB in ovine pars tuberalis is regulated both by cyclic AMP-dependent and cyclic AMP-independent mechanisms","volume":"8","author":"S McNulty","year":"1996","journal-title":"J Neuroendocrinol"},{"issue":"4","key":"pone.0255249.ref029","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/endo.139.4.5879","article-title":"Evidence that melatonin acts in the premammillary hypothalamic area to control reproduction in the ewe: presence of binding sites and stimulation of luteinizing hormone secretion by in situ microimplant delivery","volume":"139","author":"B Malpaux","year":"1998","journal-title":"Endocrinology"},{"issue":"2","key":"pone.0255249.ref030","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1095\/biolreprod.104.030064","article-title":"MTNR1a melatonin receptors in the ovine premammillary hypothalamus: day-night variation in the expression of the transcripts","volume":"72","author":"M Migaud","year":"2005","journal-title":"Biol Reprod"},{"key":"pone.0255249.ref031","first-page":"2231","article-title":"Seasonal regulation of reproduction in mammals","author":"B Malpaux","year":"2006","journal-title":"In: Knobil and Neill\u2019s Physiology of Reproduction"},{"key":"pone.0255249.ref032","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ygcen.2017.05.011","article-title":"Signaling pathways to and from the hypophysial pars tuberalis, an important center for the control of seasonal rhythms","volume":"258","author":"HW Korf","year":"2018","journal-title":"Gen Comp Endocrinol"},{"issue":"5","key":"pone.0255249.ref033","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/j.1476-5381.2009.00453.x","article-title":"The end of a myth: cloning and characterization of the ovine melatonin MT2 receptor: Cloning and characterization of ovine MT2","volume":"158","author":"F Cog\u00e9","year":"2009","journal-title":"Br J Pharmacol"},{"issue":"1","key":"pone.0255249.ref034","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1600-079X.2011.00856.x","article-title":"A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases: molecular details in the human pineal gland","volume":"51","author":"JH Stehle","year":"2011","journal-title":"J Pineal Res"},{"key":"pone.0255249.ref035","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1210\/endo-98-2-482","article-title":"Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens","author":"M Rollag","year":"1976","journal-title":"Endocrinology"},{"issue":"2","key":"pone.0255249.ref036","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1095\/biolreprod18.2.279","article-title":"Serum melatonin concentrations during different stages of the annual reproductive cycle in ewes","volume":"18","author":"MD Rollag","year":"1978","journal-title":"Biol Reprod"},{"key":"pone.0255249.ref037","first-page":"77","article-title":"Conditions for the use of specific antibodies for immunohistochemical visualization of serotonin and melatonin in the pineal gland of sheep.","author":"Y Tillet","year":"1986","journal-title":"C R Acad Sci III."},{"key":"pone.0255249.ref038","volume-title":"Melatonin and the mammalian pineal gland","author":"J Arendt","year":"1995","edition":"1"},{"issue":"2","key":"pone.0255249.ref039","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1677\/joe.0.1720397","article-title":"Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep","volume":"172","author":"A G\u00f3mez Brunet","year":"2002","journal-title":"J Endocrinol"},{"issue":"2","key":"pone.0255249.ref040","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/0003-2697(84)90466-4","article-title":"Lodinated melatonin: preparation and characterization of the molecular structure by mass and 1H NMR spectroscopy","volume":"142","author":"O Vakkuri","year":"1984","journal-title":"Anal Biochem"},{"issue":"1\u20112","key":"pone.0255249.ref041","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0006-8993(87)91625-8","article-title":"Hypothalarnic melatonin receptor sites revealed by autoradiography","volume":"435","author":"J Vanecek","year":"1987","journal-title":"Brain Res"},{"issue":"5","key":"pone.0255249.ref042","doi-asserted-by":"crossref","first-page":"8948","DOI":"10.3390\/ijms14058948","article-title":"New radioligands for describing the molecular pharmacology of MT1 and MT2 melatonin receptors.","volume":"14","author":"C Legros","year":"2013","journal-title":"Int J Mol Sci."},{"issue":"3","key":"pone.0255249.ref043","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0898-6568(01)00240-6","article-title":"Melatonin MT1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins","volume":"14","author":"ASL Chan","year":"2002","journal-title":"\u200eCell signalling"},{"issue":"24","key":"pone.0255249.ref044","doi-asserted-by":"crossref","first-page":"16762","DOI":"10.1074\/jbc.M802069200","article-title":"The PDZ protein Mupp1 promotes Gi coupling and signaling of the MT 1 melatonin receptor","volume":"283","author":"JL Guillaume","year":"2008","journal-title":"J Biol Chem"},{"issue":"21","key":"pone.0255249.ref045","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1038\/emboj.2010.236","article-title":"Molecular organization and dynamics of the melatonin MT1 receptor\/RGS20\/Gi protein complex reveal asymmetry of receptor dimers for RGS and Gi coupling","volume":"29","author":"P Maurice","year":"2010","journal-title":"EMBO J"},{"issue":"4","key":"pone.0255249.ref046","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12641","article-title":"Melatonin MT1 and MT2 receptor ERK signaling is differentially dependent on Gi\/o and Gq\/11 proteins","volume":"68","author":"M Chen","year":"2020","journal-title":"J Pineal Res"},{"issue":"3","key":"pone.0255249.ref047","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/PL00004956","article-title":"Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor","volume":"355","author":"ML Dubocovich","year":"1997","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"issue":"12","key":"pone.0255249.ref048","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1096\/fasebj.12.12.1211","article-title":"Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms","volume":"12","author":"ML Dubocovich","year":"1998","journal-title":"FASEB J"},{"issue":"5","key":"pone.0255249.ref049","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/sj.bjp.0703130","article-title":"Pharmacological characterization of human recombinant melatonin MT1 and MT2 receptors","volume":"129","author":"C Browning","year":"2000","journal-title":"Br J Pharmacol"},{"issue":"3","key":"pone.0255249.ref050","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1600-079X.1991.tb00828.x","article-title":"beta-adrenergic stimulation increases cAMP and melatonin production in ovine pinealocyte cultures","volume":"10","author":"HE Howell","year":"1991","journal-title":"J Pineal Res"},{"issue":"2","key":"pone.0255249.ref051","first-page":"115","article-title":"Molecular components and mechanism of adrenergic signal transduction in mammalian pineal gland: regulation of melatonin synthesis","volume":"43","author":"BB Gupta","year":"2005","journal-title":"Indian J Exp Biol"},{"key":"pone.0255249.ref052","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ygcen.2018.07.010","article-title":"Melatonin synthesis and clock gene regulation in the pineal organ of teleost fish compared to mammals: similarities and differences","volume":"279","author":"S Saha","year":"2019","journal-title":"Gen Comp Endocrinol"},{"issue":"6","key":"pone.0255249.ref053","doi-asserted-by":"crossref","first-page":"e1001347","DOI":"10.1371\/journal.pbio.1001347","article-title":"Circadian-related heteromerization of adrenergic and dopamine D4 receptors modulates melatonin synthesis and release in the pineal gland","volume":"10","author":"S Gonz\u00e1lez","year":"2012","journal-title":"PLoS Biol"},{"key":"pone.0255249.ref054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/715708","article-title":"Adrenergic activation of melatonin secretion in ovine pineal explants in short-term superfusion culture occurs via protein synthesis independent and dependent phenomena","volume":"2014","author":"B Lewczuk","year":"2014","journal-title":"Biomed Res. Int"},{"issue":"3","key":"pone.0255249.ref055","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1600-079X.2007.00525.x","article-title":"MT1 melatonin receptor internalization underlies melatonin-induced morphologic changes in chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1\/2 and microtubule modulation","volume":"44","author":"CD Bondi","year":"2008","journal-title":"J Pineal Res"},{"issue":"4","key":"pone.0255249.ref056","first-page":"1","article-title":"The melatonin signaling pathway in a long-term memory in vitro study.","volume":"23","author":"JY Sung","year":"2018","journal-title":"Molecules"},{"issue":"1","key":"pone.0255249.ref057","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1210\/endo.137.1.8536615","article-title":"Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine pituitary: interactions between melatonin, insulin-like growth factor-l, and forskolin","volume":"137","author":"DG Hazlerigg","year":"1996","journal-title":"Endocrinology"},{"issue":"3\u20114","key":"pone.0255249.ref058","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.anireprosci.2010.10.007","article-title":"Functional characterization of polymorphic variants for ovine MT1 melatonin receptors: possible implication for seasonal reproduction in sheep","volume":"122","author":"E Trecherel","year":"2010","journal-title":"Anim Reprod Sci"},{"issue":"10","key":"pone.0255249.ref059","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1016\/j.bcp.2008.02.022","article-title":"Molecular cloning and pharmacological characterization of rat melatonin MT1 and MT2 receptors","volume":"75","author":"V Audinot","year":"2008","journal-title":"Biochem Pharmacol"},{"issue":"4","key":"pone.0255249.ref060","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.bcp.2003.09.037","article-title":"Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors","volume":"67","author":"F Mailliet","year":"2004","journal-title":"Biochem Pharmacol"},{"key":"pone.0255249.ref061","first-page":"13","article-title":"Evidence for implication of tryptophan hydroxylase in the regulation of melatonin synthesis in ovine pinealocytes in culture","author":"K Privat","year":"2002","journal-title":"Cell Mol Neurobiol"},{"issue":"4","key":"pone.0255249.ref062","first-page":"731","article-title":"Serum melatonin and pineal indoleamine metabolism in a species with a small day\/night N-Acetyltransferase rhythm","volume":"80B","author":"M Namboodiri","year":"1985","journal-title":"Comp Biochem Physiol"},{"issue":"3","key":"pone.0255249.ref063","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1111\/j.1471-4159.1985.tb04069.x","article-title":"Rapid nocturnal increase in ovine pineal N-Acetyltransferase activity and melatonin synthesis: effects of cycloheximide","volume":"45","author":"MA Namboodiri","year":"1985","journal-title":"J Neurochem"},{"issue":"3","key":"pone.0255249.ref064","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/j.1471-4159.1985.tb12881.x","article-title":"Ovine pineal indoles: effects of L-tryptophan or L-5-hydroxytryptophan administration","volume":"44","author":"D Sugden","year":"1985","journal-title":"J Neurochem"},{"issue":"5","key":"pone.0255249.ref065","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1046\/j.1365-2826.1996.04667.x","article-title":"Pineal microdialysis of the melatonin in conscious sheep: methodology, application to a diurnal rhythm and effect of isoproterenol","volume":"8","author":"JP Ravault","year":"1996","journal-title":"J Neuroendocrinol"},{"issue":"1","key":"pone.0255249.ref066","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1600-079X.2011.00880.x","article-title":"Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland: novel regulatory principles in human melatonin synthesis","volume":"51","author":"E Maronde","year":"2011","journal-title":"J Pineal Res"},{"issue":"4","key":"pone.0255249.ref067","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1073\/pnas.0406871102","article-title":"Melatonin synthesis: 14-3-3-dependent activation and inhibition of Arylalkylamine N-Acetyltransferase mediated by phosphoserine-205","volume":"102","author":"S Ganguly","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"issue":"9","key":"pone.0255249.ref068","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/j.1365-2826.2004.01228.x","article-title":"Activation of Arylalkylamine N-Acetyltransferase by phorbol esters in bovine pinealocytes suggests a novel regulatory pathway in melatonin synthesis","volume":"16","author":"C Schomerus","year":"2004","journal-title":"J Neuroendocrinol"},{"issue":"9\u201110","key":"pone.0255249.ref069","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.lfs.2007.12.011","article-title":"Tryptophan hydroxylase is modulated by L-type calcium channels in the rat pineal gland","volume":"82","author":"R Barbosa","year":"2008","journal-title":"Life Sciences"},{"issue":"6","key":"pone.0255249.ref070","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/cbf.1270","article-title":"Effects of the blockade of high voltage-activated calcium channels onin vitro pineal melatonin synthesis","volume":"24","author":"SC Afeche","year":"2006","journal-title":"Cell Biochem Funct"},{"issue":"3","key":"pone.0255249.ref071","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1046\/j.1471-4159.2002.00839.x","article-title":"Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture: Exocytosis of 5-HT from rat pinealocytes","volume":"81","author":"H Yamada","year":"2002","journal-title":"J Neurochem"},{"issue":"13","key":"pone.0255249.ref072","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.1523\/JNEUROSCI.18-13-04946.1998","article-title":"Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and inhibits melatonin synthesis in rat pinealocytes","volume":"18","author":"H Yamada","year":"1998","journal-title":"J Neurosci"},{"issue":"6","key":"pone.0255249.ref073","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1523\/JNEUROSCI.18-06-02056.1998","article-title":"Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes","volume":"18","author":"H Yamada","year":"1998","journal-title":"J Neurosci"},{"issue":"1","key":"pone.0255249.ref074","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00441-002-0580-5","article-title":"The anatomy and innervation of the mammalian pineal gland","volume":"309","author":"M M\u00f8ller","year":"2002","journal-title":"Cell Tissue Res"},{"issue":"10","key":"pone.0255249.ref075","first-page":"1","article-title":"Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression","volume":"13","author":"JC Mays","year":"2018","journal-title":"PLoS ONE"},{"issue":"5","key":"pone.0255249.ref076","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1210\/en.2015-1888","article-title":"Melatonin synthesis: Acetylserotonin o-Methyltransferase (ASMT) is strongly expressed in a subpopulation of pinealocytes in the male rat pineal gland.","volume":"157","author":"MF Rath","year":"2016","journal-title":"Endocrinology"},{"issue":"8","key":"pone.0255249.ref077","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1523\/JNEUROSCI.16-08-02553.1996","article-title":"Astrocytes protect neurons from hydrogen peroxide toxicity","volume":"16","author":"S Desagher","year":"1996","journal-title":"J Neurosci"},{"issue":"1","key":"pone.0255249.ref078","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1146\/annurev.physiol.63.1.795","article-title":"Dynamic signaling between astrocytes and neurons","volume":"63","author":"A Araque","year":"2001","journal-title":"Annu Rev Physiol"},{"issue":"5","key":"pone.0255249.ref079","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1177\/1073858405278321","article-title":"Reactive astrocytes in neural repair and protection.","volume":"11","author":"MV Sofroniew","year":"2005","journal-title":"Neuroscientist"},{"issue":"35","key":"pone.0255249.ref080","first-page":"1","article-title":"Advances in astrocyte computational models: from metabolic reconstructions to multi-omic approaches.","volume":"14","author":"J Gonz\u00e1lez","year":"2020","journal-title":"Front Neuroinform."},{"issue":"5","key":"pone.0255249.ref081","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/00005072-198509000-00004","article-title":"Immunocytochemistry of pineal astrocytes: species differences and functional implications","volume":"44","author":"X Zang","year":"1985","journal-title":"J Neuropathol Exp Neurol"},{"key":"pone.0255249.ref082","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/618432","article-title":"Modulation of pineal melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through NF- \u03ba B activation","volume":"2013","author":"D Villela","year":"2013","journal-title":"Biomed Res Int"},{"issue":"42","key":"pone.0255249.ref083","first-page":"1","article-title":"Astrocytic-neuronal-astrocytic pathway selection for formation and degradation of glutamate\/GABA.","volume":"5","author":"L Hertz","year":"2014","journal-title":"Front Endocrinol"},{"issue":"3","key":"pone.0255249.ref084","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/glia.10109","article-title":"Functional melatonin receptors and metabolic coupling in cultured chick astrocytes","volume":"39","author":"A Adachi","year":"2002","journal-title":"Glia"},{"issue":"18","key":"pone.0255249.ref085","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1097\/00001756-199812210-00011","article-title":"Melatonin receptor subtype expression in human cerebellum","volume":"9","author":"WM Al-Ghoul","year":"1998","journal-title":"NeuroReport"},{"issue":"2","key":"pone.0255249.ref086","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1017\/S1740925X0700066X","article-title":"Cerebellar Bergmann glia: an important model to study neuron-glia interactions","volume":"3","author":"E L\u00f3pez-Bayghen","year":"2007","journal-title":"Neuron Glia Biol"}],"container-title":["PLOS 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