NPR - natriuretic peptide receptor | Elisa - Clia - Antibody - Protein

Background

Natriuretic peptide receptors (NPRs) are critical components of the cardiovascular and renal systems. These receptors bind natriuretic peptides, which are hormones involved in the regulation of blood pressure, blood volume, and sodium balance. NPRs play essential roles in cardiovascular homeostasis by mediating the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They are distributed throughout the body, with high concentrations in the kidneys, heart, lungs, and vascular endothelial cells.

Protein Structure

Natriuretic peptide receptors are transmembrane proteins characterized by:

• Extracellular ligand-binding domain: This domain binds natriuretic peptides with high affinity.
• Transmembrane domain: Anchors the receptor in the cell membrane.
• Intracellular kinase-like homology domain (KHD): Although it lacks kinase activity, it plays a role in signal transduction.
• Guanylyl cyclase domain: Responsible for converting GTP to cGMP upon ligand binding, leading to downstream signaling effects. NPRs exhibit significant structural homology but differ in their functional domains and specific ligand affinities.

Classification and Subtypes

NPRs are classified into three main types based on their structure and function:

• NPR-A (NPR1): Binds ANP and BNP, leading to increased production of cyclic GMP (cGMP), which mediates vasodilation and diuresis.
• NPR-B (NPR2): Primarily binds CNP and also activates guanylyl cyclase to produce cGMP, playing a key role in endochondral ossification and vascular relaxation.
• NPR-C (NPR3): Acts primarily as a clearance receptor, binding all natriuretic peptides and facilitating their degradation, thus modulating their levels in circulation.

Function and Biological Significance

NPRs are vital for several physiological processes:

• Blood Pressure Regulation: By promoting vasodilation and natriuresis, NPRs help reduce blood pressure.
• Volume Homeostasis: NPRs facilitate the excretion of sodium and water, thus controlling blood volume.
• Cardiovascular Protection: NPR signaling pathways protect against cardiac hypertrophy and fibrosis.
• Bone Growth: Particularly through NPR-B and CNP, these receptors influence bone development and growth plate regulation.

Clinical Issues

Dysfunction or mutations in NPR genes can lead to several clinical conditions:

• Hypertension: Impaired NPR function can contribute to elevated blood pressure and associated cardiovascular diseases.
• Heart Failure: Altered levels of natriuretic peptides and NPR activity are markers and potential therapeutic targets in heart failure.
• Skeletal Dysplasias: Mutations in NPR-B (NPR2) can cause skeletal abnormalities such as acromesomelic dysplasia, type Maroteaux.
• Renal Disorders: Abnormal NPR function can affect kidney function, leading to issues with fluid and electrolyte balance.

Summary

Natriuretic peptide receptors are crucial for maintaining cardiovascular and renal homeostasis. They mediate the effects of natriuretic peptides, influencing blood pressure, blood volume, and bone growth. NPRs are classified into three main types (NPR-A, NPR-B, and NPR-C), each with distinct functions and ligand affinities. Disruptions in NPR signaling can lead to various diseases, including hypertension, heart failure, and skeletal dysplasias. Understanding NPR structure and function provides insights into potential therapeutic approaches for these conditions.