No, AT2 Receptor and Angiotensin II Are Not the Same
The AT2 receptor (angiotensin II type 2 receptor) is a G-protein coupled receptor that binds to angiotensin II, which is a peptide hormone—they are fundamentally different molecular entities where angiotensin II is the ligand and AT2 is one of its receptors. 1
Key Distinctions
Angiotensin II (The Ligand)
- Angiotensin II is the main effector peptide of the renin-angiotensin system (RAS), functioning as a hormone that circulates in blood and acts on target tissues 1
- It is generated primarily by ACE and chymase enzymes in humans, compartmentalized in blood and tissue 1
- Angiotensin II is a peptide molecule with specific amino acid sequences at positions that determine receptor binding 2
AT2 Receptor (One of Two Receptor Types)
- The AT2 receptor is a G-protein coupled receptor (GPCR) isoform that serves as one of two major receptor subtypes for angiotensin II 1
- AT2 receptors are distinct proteins expressed on cell membranes (including nuclear and mitochondrial membranes) that bind angiotensin II 1
- The other major receptor subtype is AT1 receptor (AT1R), which mediates most classical actions of angiotensin II 1
Functional Relationship
Opposing Physiological Effects
- AT2 receptor activation by angiotensin II produces effects opposite to AT1 receptor activation, including reduced blood pressure, natriuresis, and diminished end organ damage such as fibrosis 1
- AT1 receptors mediate vasoconstriction, growth promotion, and the classical pressor effects of angiotensin II 1, 3
Binding Characteristics
- Both AT1 and AT2 receptors have identical affinity for angiotensin II despite sharing only 34% amino acid homology 4
- The molecular recognition mechanism differs substantially between the two receptor subtypes—modifications of angiotensin II side chains affect AT2 binding more uniformly across all positions, while AT1 binding is particularly dependent on specific positions (2,4,6, and 7) 2
Clinical Relevance
Receptor Distribution
- AT1 receptors are broadly expressed in afferent and efferent arterioles, glomeruli, and proximal tubules in adults 1, 3
- AT2 receptors are expressed at very high levels in the developing fetus but at much lower levels in adult cardiovascular systems 5
- AT2 receptor expression can be upregulated in pathological states associated with tissue remodeling or inflammation 5
Therapeutic Implications
- When AT1 receptor antagonists (ARBs) are used clinically, plasma angiotensin II levels rise, which then selectively stimulates AT2 receptors 6
- This selective AT2 stimulation may provide protective cardiovascular and renal effects through inhibition of AT1-mediated proliferative and fibrotic actions 5, 6