Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension

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Reyes Resina, Irene and Alkozi, Hanan Awad and Ser-Badia, Anna, del and Sánchez Naves, Juan and Lillo, Jaume and Jiménez Cano, Jasmina and Pintor, Jesús and Navarro Brugal, Gemma and Franco Fernández, Rafael (2020) Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension. Cells, 9 (1). p. 152. ISSN 2073-4409

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Official URL: https://doi.org/10.3390/cells9010152




Abstract

Background: Experiments in the late nineties showed an inverse relationship in the eye levels of melatonin and dopamine, thereby constituting an example of eye parameters that are prone to circadian variations. The underlying mechanisms are not known but these relevant molecules act via specific cell surface dopamine and melatonin receptors. This study investigated whether these receptors formed heteromers whose function impact on eye physiology. We performed biophysical assays to identify interactions in heterologous systems. Particular heteromer functionality was detected using Gi coupling, MAPK activation, and label-free assays. The expression of the heteroreceptor complexes was assessed using proximity ligation assays in cells producing the aqueous humor and human eye samples. Dopamine D3 receptors (D3Rs) were identified in eye ciliary body epithelial cells. We discovered heteromers formed by D3R and either MT1 (MT1R) or MT2 (MT2R) melatonin receptors. Heteromerization led to the blockade of D3R-Gi coupling and regulation of signaling to the MAPK pathway. Heteromer expression was negatively correlated with intraocular hypertension. Conclusions: Heteromers likely mediate melatonin and dopamine actions in structures regulating intraocular pressure. Significant expression of D3R–MT1R and D3R–MT1R was associated with normotensive conditions, whereas expression diminished in a cell model of hypertension. A clear trend of expression reduction was observed in samples from glaucoma cases. The trend was marked but no statistical analysis was possible as the number of available eyes was 2.


Item Type:Article
Additional Information:

Received: 20 November 2019 / Accepted: 2 January 2020 / Published: 8 January 2020
In memoriam of our co-author Jesús Pintor

Uncontrolled Keywords:Circadian rhythm; Glaucoma; G-protein-coupled receptor GPCR heteromer; Melatonin MT1 and MT2 receptors; G protein coupling; Mitogen-activated protein kinase pathway (MAPK); Label-free dynamic mass redistribution (DMR); Retina; Human 59HCE cells
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Optics > Eyes anatomy
ID Code:58896
Deposited On:24 Feb 2020 15:46
Last Modified:24 Feb 2020 16:14

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