RT Journal Article
T1 Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension
A1 Reyes Resina, Irene
A1 Alkozi, Hanan Awad
A1 Ser Badia, Anna Del
A1 Sánchez Naves, Juan
A1 Lillo, Jaume
A1 Jiménez Cano, Jasmina
A1 Pintor Just, Jesús Jerónimo
A1 Navarro Brugal, Gemma
A1 Franco Fernández, Rafael
AB 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.
PB MDPI
SN 2073-4409
YR 2020
FD 2020-01-08
LK https://hdl.handle.net/20.500.14352/6045
UL https://hdl.handle.net/20.500.14352/6045
LA eng
NO Reyes Resina, I., Alkozi, H. A., Ser Badia, A. et al. «Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension». Cells, vol. 9, n.o 1, enero de 2020, p. 152. DOI.org (Crossref), https://doi.org/10.3390/cells9010152.
NO In memoriam of our co-author Jesús Pintor
NO Ministerio de Economía, Comercio y Empresa (España)
NO Ministerio de Sanidad (España)
NO Gobierno de Arabia Saudí
DS Docta Complutense
RD 7 abr 2025