{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:35:08Z","timestamp":1791300908130,"version":"4.1.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T00:00:00Z","timestamp":1340064000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"DOI":"10.1371\/journal.pbio.1001347","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T17:17:06Z","timestamp":1340126226000},"page":"e1001347","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":146,"title":["Circadian-Related Heteromerization of Adrenergic and Dopamine D4 Receptors Modulates Melatonin Synthesis and Release in the Pineal Gland"],"prefix":"10.1371","volume":"10","author":[{"given":"Sergio","family":"Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moreno-Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"P\u00e9rez-Capote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Franco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"Mallol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicent","family":"Casad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carme","family":"Llu\u00eds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Ferr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Canela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1152\/physrev.1998.78.1.189","article-title":"Dopamine receptors: from structure to function.","volume":"78","author":"C Missale","year":"1998","journal-title":"Physiol Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tips.2007.10.001","article-title":"Neuronal Gq\/11-coupled dopamine receptors: an uncharted role for dopamine.","volume":"28","author":"A. J Rashid","year":"2007","journal-title":"Trends Pharmacol Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.coph.2009.09.011","article-title":"Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms.","volume":"10","author":"A Hasbi","year":"2010","journal-title":"Curr Opin Pharmacol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1755-5949.2010.00228.x","article-title":"Dopamine receptor homooligomers and heterooligomers in schizophrenia.","volume":"17","author":"M. L Perreault","year":"2011","journal-title":"CNS Neurosci Ther"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/350610a0","article-title":"Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.","volume":"350","author":"H. H Van Tol","year":"1991","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1007\/s00018-010-0293-y","article-title":"The dopamine D4 receptor: biochemical and signalling properties.","volume":"67","author":"P Rondou","year":"2010","journal-title":"Cell Mol Life Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.brainres.2008.02.025","article-title":"Dopamine D4 receptors regulate intracellular calcium concentration in cultured chicken cone photoreceptor cells: relationship to dopamine receptor-mediated inhibition of cAMP formation.","volume":"1207","author":"T. N Ivanova","year":"2008","journal-title":"Brain Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.mce.2009.05.013","article-title":"Thyroid hormone and adrenergic signaling interact to control pineal expression of the dopamine receptor D4 gene (Drd4).","volume":"314","author":"J-S Kim","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.brainres.2008.01.073","article-title":"Daily oscillation of gene expression in the retina is phase-advanced with respect to the pineal gland.","volume":"1203","author":"L Bai","year":"2008","journal-title":"Brain Research"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/0016-6480(89)90006-3","article-title":"Effect of environmental temperature and photoperiod on the melatonin levels in the pineal, lateral eye, and plasma of the frog, Rana perezi: importance of ocular melatonin.","volume":"75","author":"M. J Delgado","year":"1989","journal-title":"Gen Comp Endocrinol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1139\/y90-014","article-title":"Response to pinealectomy and blinding in vitellogenic female frogs (Rana perezi) subjected to high temperature in autumn.","volume":"68","author":"A. L Alonso-G\u00f3mez","year":"1990","journal-title":"Can J Physiol Pharmacol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00441-002-0579-y","article-title":"Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation.","volume":"309","author":"S Ganguly","year":"2002","journal-title":"Cell Tissue Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.3109\/07420528.2010.496911","article-title":"Melatonin-synthesizing enzymes in pineal, retina, liver, and gut of the goldfish (Carassius): mRNA expression pattern and regulation of daily rhythms by lighting conditions.","volume":"27","author":"E Velarde","year":"2010","journal-title":"Chronobiol Int"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.mce.2009.07.010","article-title":"Pineal function: impact of microarray analysis.","volume":"314","author":"D. C Klein","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jcb.240440105","article-title":"mRNA transcription determines the lag period for the induction of pineal melatonin synthesis in the Syrian hamster pineal gland.","volume":"44","author":"A Gonzalez-Brito","year":"1990","journal-title":"J Cell Biochem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.2174\/0929867023370013","article-title":"Serotonin N-acetyltransferase: mechanism and inhibition.","volume":"9","author":"W Zheng","year":"2002","journal-title":"Curr Med Chem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1074\/jbc.R600036200","article-title":"Arylalkylamine N-acetyltransferase: \u201cthe Timezyme.\u201d","volume":"282","author":"D. C Klein","year":"2007","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1471-4159.2009.06457.x","article-title":"Modulation of Aanat gene transcription in the rat pineal gland.","volume":"112","author":"A. K Ho","year":"2010","journal-title":"J Neurochem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.tins.2007.07.001","article-title":"Functional relevance of neurotransmitter receptor heteromers in the central nervous system.","volume":"30","author":"S Ferr\u00e9","year":"2007","journal-title":"Trends Neurosci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/sj.embor.7400052","article-title":"Roles of G-protein-coupled receptor dimerization.","volume":"5","author":"S Terrillon","year":"2004","journal-title":"EMBO Rep"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tips.2005.01.004","article-title":"Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation.","volume":"26","author":"S Bulenger","year":"2005","journal-title":"Trends Pharmacol Sci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"9050","DOI":"10.1073\/pnas.0501112102","article-title":"A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers.","volume":"102","author":"M Waldhoer","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1124\/pr.110.002667","article-title":"Allostery at G protein-coupled receptor homo- and heteromers: uncharted pharmacological landscapes.","volume":"62","author":"N. J Smith","year":"2010","journal-title":"Pharmacol Rev"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.neuron.2011.10.038","article-title":"Apo-ghrelin receptor forms heteromers with DRD2 in hypothalamic neurons and is essential for anorexigenic effects of DRD2 agonism.","volume":"73","author":"A Kern","year":"2012","journal-title":"Neuron"},{"key":"ref25","article-title":"CXCR7\/CXCR4 heterodimer constitutively recruits {beta}-arrestin to enhance cell migration. J Biol Chem 286: 32188\u201332197.","author":"F. M Decaillot","year":"2011"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"7412","DOI":"10.1523\/JNEUROSCI.0191-11.2011","article-title":"Dopamine-galanin receptor heteromers modulate cholinergic neurotransmission in the rat ventral hippocampus.","volume":"31","author":"E Moreno","year":"2011","journal-title":"J Neurosci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.neuron.2010.12.001","article-title":"Facilitation of \u03bc-opioid receptor activity by preventing \u03b4-opioid receptor-mediated codegradation.","volume":"69","author":"S-Q He","year":"2011","journal-title":"Neuron"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/nm.2263","article-title":"Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects.","volume":"16","author":"L Pei","year":"2010","journal-title":"Nat Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.tips.2011.05.006","article-title":"Asymmetry of GPCR oligomers supports their functional relevance.","volume":"32","author":"P Maurice","year":"2011","journal-title":"Trends Pharmacol Sci"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nchembio0309-131","article-title":"Building a new conceptual framework for receptor heteromers.","volume":"5","author":"S Ferr\u00e9","year":"2009","journal-title":"Nat Chem Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.exer.2008.08.004","article-title":"Localization and regulation of dopamine receptor D4 expression in the adult and developing rat retina.","volume":"87","author":"L. L Klitten","year":"2008","journal-title":"Exp Eye Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.physiol.69.022405.154749","article-title":"\u03b2-arrestins and cell signaling.","volume":"69","author":"S. M DeWire","year":"2007","journal-title":"Annu Rev Physiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1021\/ac9022956","article-title":"Experimental determination of the F\u00f6rster distance for two commonly used bioluminescent resonance energy transfer pairs.","volume":"82","author":"H Dacres","year":"2009","journal-title":"Anal Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1100\/tsw.2008.136","article-title":"Detection of heteromers formed by cannabinoid CB1, dopamine D2, and adenosine A2A G-protein-coupled receptors by combining bimolecular fluorescence complementation and bioluminescence energy transfer.","volume":"8","author":"G Navarro","year":"2008","journal-title":"ScientificWorldJournal"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1210\/me.2005-0084","article-title":"Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor\/dopamine receptor subtype 1 heterodimers.","volume":"20","author":"H Jiang","year":"2006","journal-title":"Mol Endocrinol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"30062","DOI":"10.1074\/jbc.M705302200","article-title":"Allosteric transinhibition by specific antagonists in CCR2\/CXCR4 heterodimers.","volume":"282","author":"D Sohy","year":"2007","journal-title":"J Biol Chem"},{"key":"ref37","article-title":"CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signalling. Blood 113: 6085\u20136093","author":"A Levoye","year":"2009"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.1074\/jbc.M110.161489","article-title":"Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway.","volume":"286","author":"E Moreno","year":"2011","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"26128","DOI":"10.1074\/jbc.M000345200","article-title":"Oligomerization of \u03bc- and \u03b4-opioid receptors.","volume":"275","author":"S. R George","year":"2000","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1073\/pnas.0604049104","article-title":"D1\u2013D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq\/11 in the striatum.","volume":"104","author":"A. J Rashid","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1038\/sj.emboj.7601193","article-title":"The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization.","volume":"25","author":"A Levoye","year":"2006","journal-title":"EMBO J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2144\/000113719","article-title":"Detection of antigen interactions ex vivo by proximity ligation assay: endogenous dopamine D2-adenosine A2A receptor complexes in the striatum.","volume":"51","author":"P Trifilieff","year":"2011","journal-title":"BioTechniques"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ymeth.2008.06.014","article-title":"Characterizing proteins and their interactions in cells and tissues using the in situ proximity ligation assay.","volume":"45","author":"O S\u00f6derberg","year":"2008","journal-title":"Methods"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nmeth.1229","article-title":"Detection of heteromerization of more than two proteins by sequential BRET-FRET.","volume":"5","author":"P Carriba","year":"2008","journal-title":"Nat Methods"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1476-5381.2009.00152.x","article-title":"Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors.","volume":"157","author":"C Ferrada","year":"2009","journal-title":"Br J Pharmacol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"18676","DOI":"10.1073\/pnas.1008911107","article-title":"Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine.","volume":"107","author":"G Navarro","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1038\/emboj.2011.143","article-title":"The oligomeric state sets GABAB receptor signalling efficacy.","volume":"30","author":"L Comps-Agrar","year":"2011","journal-title":"EMBO J"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.tips.2009.01.003","article-title":"The apparent cooperativity of some GPCRs does not necessarily imply dimerization.","volume":"30","author":"M Chabre","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1124\/jpet.111.179093","article-title":"Heteromerization of the {micro}- and {delta}-opioid receptors produces ligand-biased antagonism and alters {micro}-receptor trafficking.","volume":"337","author":"L Milan-Lobo","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"ref50","first-page":"307","article-title":"The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland.","volume":"52","author":"D. C Klein","year":"1997"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1600-079X.1997.tb00337.x","article-title":"The role of the intracellular and extracellular serotonin in the regulation of melatonin production in rat pinealocytes.","volume":"23","author":"J. M Miguez","year":"1997","journal-title":"J Pineal Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1124\/pr.55.2.2","article-title":"Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters.","volume":"55","author":"V Simonneaux","year":"2003","journal-title":"Pharmacol Rev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1111\/j.1471-4159.1990.tb04952.x","article-title":"5-Hydroxytryptamine amplifies beta-adrenergic stimulation of N-acetyltransferase activity in rat pinealocytes.","volume":"55","author":"D Sugden","year":"1990","journal-title":"J Neurochem"},{"key":"ref54","first-page":"183","article-title":"TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway.","volume":"49","author":"S Da Silveira Cruz-Machado","year":"2010","journal-title":"J Pineal Res"}],"container-title":["PLoS Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pbio.1001347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T23:01:03Z","timestamp":1642546863000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.1001347"}},"subtitle":[],"editor":[{"given":"Ueli","family":"Schibler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,6,19]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2012,6,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.1001347","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717951608.793456910","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.717951608.793461411","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,19]]}}}