Endothelin Subtypes and Distribution

Endothelins (ETs) are a family of potent vasoactive peptides originally identified in porcine aortic endothelial cells. Each ET peptide consists of 21 amino acids with a hydrophobic C-terminus and two intra-chain disulfide bonds, conferring strong vasoconstrictive properties. In humans, three ET isoforms have been identified: ET-1, ET-2, and ET-3. While all three act as potent arterial smooth muscle constrictors in vitro, their vasoconstrictive potency follows the order ET-2 > ET-1 > ET-3, reflecting differences in peptide hydrophobicity and structural properties.

ETs are broadly distributed across multiple organs and systems, but each isoform exhibits distinct tissue specificity. ET-1 is synthesized by nearly all cell types and is highly expressed in endothelial cells, where its production is rapidly upregulated in response to stimuli such as hypoxia, ischemia, and shear stress. ET-2 is primarily found in the kidney and small intestine, contributing to processes such as alveolar development and intestinal contraction. ET-3 shows more restricted distribution and is particularly important in neural crest-derived tissues.