A novel potent vasoconstrictor peptide produced by vascular endothelial cells

Why this mattered

Yanagisawa et al. (1988) changed vascular biology by showing that endothelial cells were not only a passive lining or a source of relaxing signals such as prostacyclin and endothelium-derived relaxing factor, but could also generate an exceptionally potent constrictor signal. The paper isolated a 21-residue peptide, named endothelin, from endothelial-cell culture medium, showed strong vasoconstrictor activity, and cloned the precursor cDNA. That combination made endothelin immediately legible as a regulated molecular system rather than just an unexplained bioassay activity.

What became possible afterward was an entire research program: tracing endothelin synthesis from preproendothelin through proteolytic processing, identifying endothelin isoforms, cloning ETA and ETB receptors, and mapping endothelin signaling across vascular smooth muscle, kidney, lung, heart, nervous-system development, and disease. The discovery helped reframe vascular tone as a balance of endothelial dilator and constrictor programs, with gene regulation and receptor pharmacology at its center. It also provided a concrete therapeutic target: later endothelin-receptor antagonists, most prominently in pulmonary arterial hypertension, descend directly from the pathway this paper made visible.

Abstract

(no abstract available)

Related

• cite → Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor — The endothelin paper contrasts its endothelial vasoconstrictor peptide with nitric oxide as the endothelium-derived relaxing factor.
• cite → DNA sequencing with chain-terminating inhibitors — The endothelin paper used Sanger chain-termination DNA sequencing to determine the nucleotide sequence encoding the peptide precursor.
• cite → The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine — Yanagisawa et al. build on Furchgott and Zawadzki's endothelium-dependent vascular regulation by identifying endothelin as an endothelial-cell-derived vasoconstrictor peptide.
• enables ← DNA sequencing with chain-terminating inhibitors — Sanger sequencing enabled identification of the amino-acid sequence of endothelin, the endothelial vasoconstrictor peptide reported in 1988.
• enables ← The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine — The discovery of endothelium-dependent relaxation established endothelial cells as active vascular regulators, setting up the search for endothelial constrictor factors like endothelin.

Sources

• DOI: https://doi.org/10.1038/332411a0
• OpenAlex: https://openalex.org/W2162804111