EFHC1

Overview

The Endothelin Receptor Type B (EDNRB) is a G protein-coupled receptor that binds to endothelins, which are potent vasoconstrictor peptides. EDNRB plays a crucial role in the regulation of vascular tone, development of neural crest-derived cells, and various physiological processes. It is encoded by the EDNRB gene located on chromosome 13 in humans.

Structure

EDNRB is a member of the endothelin receptor family, which includes Endothelin Receptor Type A (EDNRA). It is a transmembrane protein that spans the cell membrane seven times, characteristic of G protein-coupled receptors. The receptor has an extracellular N-terminus, seven transmembrane helices, and an intracellular C-terminus.

Function

EDNRB is primarily involved in:

• Vasoconstriction and Vasodilation: EDNRB mediates the effects of endothelins, leading to vasoconstriction or vasodilation depending on the tissue context.
• Neural Crest Cell Development: It is essential for the migration and differentiation of neural crest cells, which give rise to various cell types, including melanocytes and enteric neurons.
• Endothelial Cell Function: EDNRB is expressed in endothelial cells and contributes to the regulation of blood flow and vascular homeostasis.

Clinical Significance

Mutations in the EDNRB gene are associated with several disorders, including:

• Hirschsprung's Disease: A congenital condition characterized by the absence of enteric ganglia in the distal colon, leading to bowel obstruction.
• Waardenburg Syndrome: A genetic disorder that can cause hearing loss and changes in pigmentation of the hair, skin, and eyes.

Pathophysiology

The dysfunction of EDNRB can lead to abnormal vascular responses and contribute to the pathogenesis of diseases such as pulmonary arterial hypertension and certain types of cancer. The receptor's role in neural crest cell development also implicates it in developmental disorders.

Therapeutic Implications

Targeting EDNRB with specific antagonists or agonists is a potential therapeutic strategy for treating conditions like hypertension, cancer, and neurocristopathies. Research is ongoing to develop drugs that can modulate EDNRB activity effectively.

Research

Current research on EDNRB focuses on understanding its role in disease mechanisms, developing targeted therapies, and exploring its function in various physiological processes. Studies are also investigating the receptor's involvement in cardiovascular disease, cancer, and neurodevelopmental disorders.

Also see

• Endothelin Receptor Type A
• G protein-coupled receptor
• Hirschsprung's Disease
• Waardenburg Syndrome
• Vasoconstriction
• Neural crest