Circadian-Related Heteromerization of Adrenergic and Dopamine D4 Receptors Modulates Melatonin Synthesis and Release in the Pineal Gland

Abstract

Dopamine and adrenergic receptor complexes form under a circadian-regulated cycle and directly modulate melatonin synthesis and release from the pineal gland.

Impact of G protein-coupled receptor heteromers in endocrine systems

“…Techniques such as fluorescent correlation spectroscopy (9,10), single particle tracking via total internal-reflection fluorescent microscopy (11)(12)(13) and localization microscopy techniques such as photoactivated localization microscopy (14,15) have been utilised to identify GPCR heteromers and homomers. Likewise, proximity ligation assays (PLA), also provide a mechanism for identifying heteromers in native tissues (16).…”

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

“…GLUT1-IGF-IR interactions were detected in astrocytes grown on glass coverslips using the Duolink II in situ proximity ligation assay (PLA) detection kit (OLink AB, Uppsala, Sweden), as described previously (17). Astrocytes were fixed in 4% paraformaldehyde for 10 min, washed with PBS containing 20 mmol/L glycine to quench the aldehyde groups, permeabilized with the same buffer containing 0.05% Triton X-100 for 5 min, and successively washed with PBS.…”

Oligomerization of GPCRs involved in endocrine regulation

“…It could be hypothesized that a relevant oligomerization is dependent on a functional significance (Tadagaki et al 2012a). In case of heterodimerization, GPCR expression in the same cell type (Waldhoer et al 2005, Pin et al 2007) and simultaneous occurrence ( Gonzalez et al 2012) are prerequisites. Oligomerization has been reported for several GPCR subfamilies such as for the family A, family B or taste receptors (Li et al 2002, Harikumar et al 2008, Ng et al 2012, Ng & Chow 2015.…”

“…Moreover, the trace amineassociated receptor 1 (TAAR1) interacts, for example, with the dopamine-2 receptor (D2R) and, in turn, modifies dopaminergic neurotransmission (Harmeier et al 2015). Further examples include circadian-controlled heterodimers between the D4R and the β1-or α1B-adrenergic receptor, respectively, that are involved in the regulation of serotonin and melatonin syntheses (Gonzalez et al 2012) and the interactome of melatonin receptors involved in circadian rhythm regulation (Benleulmi-Chaachoua et al 2016).…”