Angiotensin II type 1 receptor – Dopamine D1 receptor heterodimer (AT1R-D1R heterodimer)

The Angiotensin II type 1 receptor – Dopamine D1 receptor (AT1R-D1R) heterodimer is a G protein-coupled receptor (GPCR) complex that serves as a pivotal regulator of renal sodium handling and systemic blood pressure (nih.gov, 2012). Located predominantly in the renal proximal tubule, these two receptors function as a 'unit of opposites' where AT1R mediates sodium reabsorption and D1R promotes sodium excretion (natriuresis) (ahajournals.org, 2019). Heterodimerization facilitates direct allosteric communication between the receptors, allowing the status of one to modulate the signaling efficacy and cellular trafficking of the other (nih.gov, 2008). In conditions like hypertension, the reciprocal inhibition within the heterodimer is often skewed, leading to suppressed D1R signaling and excessive AT1R-mediated sodium retention (nih.gov, 2012). Pharmacological intervention with AT1R blockers (ARBs), such as losartan, has been shown to allosterically stabilize the heterodimer in a conformation that favors D1R membrane recruitment and activation, thereby restoring natriuretic capacity (nih.gov, 2008). Consequently, the AT1R-D1R heterodimer is a significant therapeutic target for the treatment of salt-sensitive hypertension and related cardiovascular disorders (mdpi.com, 2021). This target is particularly relevant in age-related hypertension, where oxidative stress further impairs the functional balance of the complex (nih.gov, 2012).

Other names

AT1R-D1R complexAT1R-D1R heteromerAngiotensin II type 1 receptor – Dopamine D1 receptor complexAT1R-D1R heteromeric complexAngiotensin II type 1 receptor – Dopamine D1 receptor heterodimer / Dopamine D1 receptor signaling

AT1R antagonists (ARBs) like losartan act as allosteric modifiers of the AT1R-D1R heterodimer, strengthening the physical interaction and promoting the translocation of D1R to the plasma membrane, which enhances D1R-mediated cAMP signaling and natriuresis (nih.gov, 2008).