PTGIR - Prostacyclin Receptor | Elisa - Clia - Antibody - Protein

Background

PTGIR, also known as the prostacyclin receptor, is a G-protein-coupled receptor (GPCR) that mediates the effects of prostacyclin (prostaglandin I2, PGI2), a lipid-derived signaling molecule. Prostacyclin is primarily produced by endothelial cells and plays a critical role in regulating vascular homeostasis, inflammation, and platelet aggregation. By binding to PTGIR, prostacyclin activates intracellular signaling pathways that lead to vasodilation, inhibition of platelet aggregation, and modulation of immune responses. PTGIR is highly expressed in vascular smooth muscle cells, endothelial cells, and platelets, as well as in other tissues, including the lungs and kidneys. Dysregulation of PTGIR signaling is implicated in cardiovascular diseases, pulmonary hypertension, and inflammation-related disorders.

Protein Structure

PTGIR is a typical GPCR consisting of approximately 386 amino acids and characterized by the following structural features:

1. Seven-Transmembrane Domains: These helices span the plasma membrane and are essential for ligand binding and signal transduction.
2. Extracellular Domain: Contains specific binding sites for prostacyclin, enabling high-affinity ligand interaction.
3. Intracellular Loops: Facilitate coupling with G-proteins, particularly the Gs protein, which activates adenylate cyclase.
4. C-Terminal Tail: Contains phosphorylation sites for protein kinase A (PKA) and G-protein-coupled receptor kinases (GRKs), regulating receptor desensitization and internalization.
5. Ligand Binding Pocket: Unique residues within the transmembrane region contribute to selective prostacyclin recognition and receptor activation.

The structural configuration of PTGIR ensures precise signaling responses to prostacyclin binding.

Classification and Subtypes

PTGIR is part of the prostaglandin receptor family, which belongs to the class A (rhodopsin-like) GPCRs. This family includes receptors for other prostaglandins, such as EP (PGE2 receptors) and TP (thromboxane receptor). PTGIR specifically binds prostacyclin with high selectivity and does not respond to other prostaglandins under physiological conditions.

Function and Biological Significance

PTGIR mediates the diverse physiological effects of prostacyclin, including:

1. Vasodilation: PTGIR activation leads to increased cyclic AMP (cAMP) production via adenylate cyclase, resulting in smooth muscle relaxation and reduced vascular resistance.
2. Inhibition of Platelet Aggregation: Prostacyclin binding to PTGIR reduces platelet activation, preventing thrombus formation and maintaining hemostatic balance.
3. Anti-Inflammatory Effects: PTGIR modulates immune cell activity, reducing leukocyte adhesion and cytokine production, thereby dampening inflammation.
4. Pulmonary Function: In the lungs, PTGIR contributes to vasodilation and regulates vascular tone, playing a role in preventing pulmonary hypertension.
5. Cardiovascular Protection: By reducing platelet aggregation and promoting vasodilation, PTGIR protects against atherosclerosis and other cardiovascular diseases.
6. Renal Function: PTGIR is involved in regulating renal blood flow and sodium excretion, contributing to blood pressure regulation.

These functions underscore PTGIR’s critical role in maintaining vascular integrity, preventing thrombosis, and modulating inflammatory responses.

Clinical Issues

Dysregulation of PTGIR signaling is implicated in a variety of diseases:

1. Cardiovascular Diseases: Impaired PTGIR function is associated with hypertension, atherosclerosis, and thrombotic disorders, as it compromises prostacyclin-mediated vasodilation and antiplatelet effects.
2. Pulmonary Arterial Hypertension (PAH): Reduced PTGIR expression or function contributes to increased pulmonary vascular resistance, leading to PAH. Synthetic prostacyclin analogs targeting PTGIR are used as therapeutic agents in this condition.
3. Inflammatory Diseases: Dysregulated PTGIR activity exacerbates chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease.
4. Cancer: Altered PTGIR signaling may contribute to tumor progression by influencing angiogenesis and immune cell recruitment in the tumor microenvironment.
5. Platelet Disorders: Impaired PTGIR signaling leads to excessive platelet aggregation, increasing the risk of thrombotic events such as stroke and myocardial infarction.

Summary

PTGIR is a GPCR that mediates the effects of prostacyclin, regulating vascular tone, platelet aggregation, and inflammation. Its structure includes seven transmembrane domains, extracellular ligand-binding sites, and intracellular regions for G-protein coupling and signal transduction. PTGIR’s critical roles in cardiovascular protection and pulmonary function underscore its therapeutic importance. Dysregulation of PTGIR signaling contributes to conditions such as hypertension, thrombosis, PAH, and chronic inflammatory diseases, highlighting its significance as a potential drug target in cardiovascular and inflammatory disorders.