AGTR1 - Angiotensin II receptor type 1| Elisa - Clia - Antibody - Protein

Background:

AGTR1 is a G-protein-coupled receptor (GPCR) that mediates the majority of the physiological effects of angiotensin II, a key hormone in the renin-angiotensin-aldosterone system (RAAS). It is primarily expressed in tissues such as the heart, kidneys, vascular smooth muscle, and adrenal glands, where it regulates critical functions including blood pressure, fluid balance, and vascular tone. Upon activation by angiotensin II, AGTR1 initiates signaling cascades involving Gq proteins, which increase intracellular calcium levels and activate pathways such as protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) generation.

This receptor is crucial for maintaining cardiovascular homeostasis, but its overactivation contributes to conditions like hypertension, heart failure, kidney disease, and vascular remodeling. AGTR1 blockers, such as losartan and valsartan, are widely used in clinical practice to treat these disorders by inhibiting angiotensin II signaling. Dysregulation of AGTR1 is also implicated in promoting inflammation, fibrosis, and oxidative stress, further linking it to the progression of chronic diseases. Genetic polymorphisms in AGTR1 have been associated with variable risks for cardiovascular and renal diseases, highlighting its importance in personalized medicine.

Protein Structure:

• Molecular Weight: Approximately 41 kDa.
• Primary Structure: AGTR1 consists of 359 amino acids.
• Transmembrane Domains: It is a G-protein-coupled receptor (GPCR) with seven transmembrane alpha-helices.
• Ligand-Binding Sites: Specific extracellular regions are responsible for binding angiotensin II.
• Intracellular Domains: These regions interact with G-proteins and other signaling molecules to initiate intracellular signaling cascades.

Classification and Subtypes:

• GPCR Family: AGTR1 belongs to the class A (rhodopsin-like) GPCR family.
• Subtypes: There are two main subtypes of angiotensin II receptors: AT1 and AT2. AGTR1 (AT1) is the most well-characterized and is responsible for most of the known actions of angiotensin II.

Function and Biological Significance:

• Vasoconstriction: AGTR1 mediates vasoconstriction, leading to increased blood pressure.
• Aldosterone Secretion: Stimulation of AGTR1 promotes the release of aldosterone from the adrenal cortex, leading to sodium and water retention and potassium excretion.
• Cell Growth and Proliferation: AGTR1 activation can induce hypertrophy and hyperplasia of vascular smooth muscle cells.
• Inflammatory Responses: AGTR1 has roles in inflammation and fibrosis, contributing to cardiovascular remodeling and pathology.

Interactions:

• Angiotensin II: The primary ligand for AGTR1, binding to this receptor to initiate its physiological effects.
• G-Proteins: AGTR1 couples with Gq/11 proteins to activate phospholipase C, leading to increased intracellular calcium levels and activation of protein kinase C.
• β-Arrestins: These proteins can desensitize AGTR1 signaling and mediate receptor internalization and alternative signaling pathways.
• Other Receptors: AGTR1 can form heterodimers with other GPCRs, modifying its signaling properties.

Clinical Issues:

• Hypertension: Overactivation of AGTR1 is a major factor in the development of hypertension. Antagonists of AGTR1, known as ARBs (Angiotensin II Receptor Blockers), are commonly used antihypertensive drugs.
• Cardiovascular Diseases: AGTR1 is involved in the pathogenesis of heart failure, atherosclerosis, and myocardial infarction due to its roles in vasoconstriction, inflammation, and cellular proliferation.
• Kidney Diseases: AGTR1 contributes to the progression of chronic kidney disease and diabetic nephropathy through its effects on glomerular hemodynamics and fibrosis.
• Pharmacogenomics: Genetic polymorphisms in AGTR1 can influence an individual's response to ARBs and susceptibility to hypertension and cardiovascular diseases.

Summary:

The Angiotensin II receptor type 1 (AGTR1) is a critical GPCR in the renin-angiotensin system, mediating the effects of angiotensin II on blood pressure, fluid balance, and cellular growth. AGTR1's primary functions include vasoconstriction, aldosterone secretion, and regulation of cell proliferation. Dysregulation of AGTR1 signaling is implicated in hypertension, cardiovascular diseases, and kidney disorders. AGTR1 antagonists (ARBs) are effective therapeutic agents for managing these conditions, highlighting the receptor's significance in clinical medicine. Understanding AGTR1's structure, function, and interactions is essential for developing targeted therapies for related diseases.