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Circadian-related heteromerization of adrenergic and dopamine D4 receptors modulates melatonin synthesis and release in the pineal gland.

Authors: González, Sergio  Moreno-Delgado, David  Moreno, Estefanía  Pérez-Capote, Kamil  Franco, Rafael  Mallol, Josefa  Cortés, Antoni  Casadó, Vicent  Lluís, Carme  Ortiz, Jordi  Ferré, Sergi  Canela, Enric  McCormick, Peter J 
Citation: González S, etal., PLoS Biol. 2012;10(6):e1001347. doi: 10.1371/journal.pbio.1001347. Epub 2012 Jun 19.
Pubmed: (View Article at PubMed) PMID:22723743
DOI: Full-text: DOI:10.1371/journal.pbio.1001347

The role of the pineal gland is to translate the rhythmic cycles of night and day encoded by the retina into hormonal signals that are transmitted to the rest of the neuronal system in the form of serotonin and melatonin synthesis and release. Here we describe that the production of both melatonin and serotonin by the pineal gland is regulated by a circadian-related heteromerization of adrenergic and dopamine D4 receptors. Through α(1B)-D4 and ß1-D4 receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. This inhibition was not observed at hours of the day when D4 was not expressed. These data provide a new perspective on dopamine function and constitute the first example of a circadian-controlled receptor heteromer. The unanticipated heteromerization between adrenergic and dopamine D4 receptors provides a feedback mechanism for the neuronal hormone system in the form of dopamine to control circadian inputs.

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RGD Object Information
RGD ID: 13432344
Created: 2017-09-26
Species: All species
Last Modified: 2017-09-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.