Reactome | EDNRA, EDNRB bind non-selective ERAs

EDNRA, EDNRB bind non-selective ERAs

Stable Identifier

R-HSA-9731393

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

Synonyms

EDNRA, EDNRB bind EDNR antagonists

ReviewStatus

5/5

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Endothelins (EDNs) are 21-amino acid vasoconstricting peptides produced primarily in the endothelium that play a key role in vascular homeostasis. They are potent and long-lasting vasoconstrictors. An imbalance and over-expression of EDNs can contribute to hypertension (high blood pressure). EDNs bind to two endothelin receptors, EDNRA and EDNRB. EDNRA is primarily located in the smooth muscle of blood vessels and upon EDN binding, leads to vasoconstriction and sodium retention, ultimately increasing blood pressure. EDNRB is primarily located on endothelial cells lining the internal walls of vasculature. EDN binding to EDNRB leads to the release of NO (nitric oxide), a powerful vasodilator.

EDNR antagonists (ERAs) are competitive antagonists of EDNs at EDNRs. Dual-acting ERAs such as macitentan (Ahn et al. 2014) and bosentan (Clozel et al. 1994, Weber et al. 1996) can bind to both EDNRA and EDNRB receptors but have greater sensitivity for EDNRA so these drugs can be used to treat PAH (Zheng et al. 2020).

Literature References

PubMed ID	Title	Journal	Year
8823230	Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects Birnboeck, H, Hopfgartner, G, Weber, C, Peeters, PA, Schmitt, R, Jonkman, JH, Jones, CR, van Marle, SP	Clin Pharmacol Ther	1996
24906252	Pharmacokinetic-pharmacodynamic relationships of macitentan, a new endothelin receptor antagonist, after multiple dosing in healthy Korean subjects Jang, IJ, Kim, SE, Ahn, LY, Lim, KS, Dingemanse, J, Yu, KS, Yi, S	Am J Cardiovasc Drugs	2014
8035319	Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist Müller, M, Cassal, JM, Breu, V, Neidhart, W, Burri, K, Kalina, B, Hirth, G, Clozel, M, Löffler, BM, Gray, GA	J Pharmacol Exp Ther	1994