Angiotensin ii receptor
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Angiotensin II Receptor: Structure, Function, and Therapeutic Implications
Introduction to Angiotensin II Receptors
Angiotensin II (Ang II) is a critical peptide hormone in the renin-angiotensin system (RAS), playing a significant role in regulating blood pressure and cardiovascular homeostasis. Ang II exerts its effects primarily through two receptor subtypes: Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R) 123.
AT1 Receptor: Structure and Signaling Pathways
Structure of AT1 Receptor
The AT1 receptor is a seven-transmembrane G protein-coupled receptor (GPCR) predominantly expressed in adult tissues. It was first isolated through expression cloning, revealing its primary sequence and confirming its membership in the GPCR superfamily 6. The receptor's structure facilitates its interaction with various intracellular signaling molecules, leading to diverse physiological responses 25.
Signaling Mechanisms
AT1R mediates most of the known actions of Ang II, including vasoconstriction, aldosterone secretion, and cellular growth. It activates several signal transduction pathways, such as phospholipases A, C, and D, inositol phosphates, calcium channels, and various kinases 125. These pathways contribute to the receptor's role in hypertension, cardiovascular remodeling, and end-organ damage 3.
AT2 Receptor: Structure and Function
Expression and Distribution
The AT2 receptor is highly expressed during fetal development and is upregulated in pathological conditions in adults. It is found in various tissues, including the adrenals, ovaries, uterus, and brain 145.
Signaling Pathways and Biological Roles
Unlike AT1R, the AT2 receptor's signaling mechanisms are less understood. It involves serine and tyrosine phosphatases, phospholipase A2, nitric oxide, and cyclic guanosine monophosphate (cGMP) pathways 14. The AT2 receptor often counteracts the growth responses initiated by AT1R, playing roles in anti-proliferation, cellular differentiation, apoptosis, and vasodilation 479.
Therapeutic Implications
AT1 Receptor Antagonists
AT1 receptor antagonists, such as losartan, are widely used in treating hypertension and cardiovascular diseases. These antagonists are as effective as angiotensin-converting enzyme (ACE) inhibitors but are generally better tolerated 12.
AT2 Receptor Agonists
Recent studies have highlighted the therapeutic potential of AT2 receptor agonists. The discovery of nonpeptide agonist C21 has spurred research into AT2R's role in conditions like obesity, hypertension, and kidney diseases. AT2R agonists may offer new avenues for treating these conditions by leveraging the receptor's counter-regulatory effects against AT1R-mediated actions 49.
Conclusion
The angiotensin II receptors, AT1R and AT2R, play crucial roles in cardiovascular physiology and pathophysiology. While AT1R mediates most of Ang II's known effects, including vasoconstriction and cellular growth, AT2R often counteracts these effects and is involved in anti-proliferation and vasodilation. Understanding these receptors' signaling mechanisms and functions has significant therapeutic implications, particularly in developing targeted treatments for cardiovascular and renal diseases.
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International union of pharmacology. XXIII. The angiotensin II receptors.
The angiotensin II receptors play a crucial role in cardiovascular diseases, and their development has led to improved therapies for renin-angiotensin system disorders.
Highly CitedUnderstanding Angiotensin II Type 1 Receptor Signaling in Vascular Pathophysiology.
Angiotensin II Type 1 receptor signaling plays a crucial role in vascular pathophysiology, contributing to hypertension and contributing to the development of cardiovascular diseases.
Very Rigorous JournalHighly CitedAngiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.
The angiotensin II type 1 receptor (AT1R) plays a central role in cardiovascular physiology and pathophysiology, with potential therapeutic applications in treating various diseases.
Highly CitedAngiotensin II Type 2 Receptor
AT2R plays a crucial role in blood pressure regulation, obesity/metabolism, organ protection, and COVID-19 treatment, with potential applications in the future.
Very Rigorous JournalAngiotensin II receptors.
AT1 and AT2 receptors mediate various angiotensin II effects, with AT1 receptors playing a role in vasodilation and AT2 receptors affecting cell growth and fibrosis.
Highly CitedIsolation of a cDNA encoding the vascular type-1 angiotensin II receptor
The vascular AT1 receptor cDNA has been isolated, enabling structural analysis and definition of the angiotensin II receptor gene family, potentially contributing to the genetic component of hypertension.
Highly CitedThe Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone.
The crystal structure of human AT2R bound to angiotensin II reveals key residues that play a role in blood pressure regulation and can inform the design of more effective ligands for this receptor.
The Other Angiotensin II Receptor: AT2R as a Therapeutic Target.
AT2R agonists and antagonists show potential as therapeutic targets for cardiovascular diseases and pain control, but optimizing binding properties and targeting to target tissues is crucial.
Angiotensin receptors: distribution, signalling and function.
Angiotensin II receptors play a crucial role in blood pressure regulation and cardiovascular homeostasis, with the AT(1) receptor mediating most actions and the AT(2) receptor potentially playing a role in anti-proliferation, cellular differentiation, apoptosis, and vasodilatation
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