Mas proto-oncogene G protein-coupled receptor–Dopamine receptor D2 heteromer (Mas-D2R heteromer)

The Mas proto-oncogene G protein-coupled receptor–Dopamine receptor D2 (Mas-D2R) heteromer is a functional protein complex formed by the physical association of the Mas receptor (MAS1) and the Dopamine D2 receptor (D2R) (Li et al., 2014, Hypertension). This heteromer is primarily localized in the renal proximal tubule cells, where it integrates signals from the protective arm of the renin-angiotensin system and the dopaminergic system (Jose et al., 2016, Am J Physiol Renal Physiol). Its main biological role is the regulation of sodium homeostasis; simultaneous activation by ligands like Angiotensin-(1-7) and dopamine produces a synergistic natriuretic effect. This synergy occurs through the inhibition of key renal sodium transporters, including Na+/K+-ATPase and the sodium-hydrogen exchanger 3 (NHE3). Dysregulation of the Mas-D2R heteromer is associated with the development of essential hypertension and impaired renal sodium handling. As a therapeutic target, the heteromer offers a pathway for developing antihypertensive treatments that may achieve higher efficacy with lower drug doses by exploiting receptor synergy. Research indicates that pharmacological agents like the Mas agonist AVE0991 and the D2R agonist quinpirole can modulate this complex to enhance renal function.

Other names

MAS1-DRD2 heteromerMas-D2 receptor complexAngiotensin-(1-7) receptor-Dopamine D2 receptor heteromer

The heteromer facilitates synergistic signaling between the Mas receptor and Dopamine D2 receptor, leading to the inhibition of renal sodium transporters such as Na+/K+-ATPase and NHE3, which promotes sodium excretion and reduces blood pressure (Li et al., 2014, Hypertension).