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

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 and McCormick, Peter J (2012) Circadian-related heteromerization of adrenergic and dopamine D₄ receptors modulates melatonin synthesis and release in the pineal gland. PLoS Biology, 10 (6). ISSN 1545-7885

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Abstract

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 β₁-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.

Item Type: Article
Additional Information: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Uncontrolled Keywords: animals,cho cells,circadian rhythm,cricetinae,dopamine,hek293 cells,humans,male,melatonin,pineal gland,rats,receptors, adrenergic, alpha-1,receptors, adrenergic, beta-1,receptors, dopamine d4,serotonin,transfection
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 13 Jan 2014 13:14
Last Modified: 13 Jul 2020 23:42
URI: https://ueaeprints.uea.ac.uk/id/eprint/47152
DOI: 10.1371/journal.pbio.1001347

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