ET-1（Endothelin-1）
ET-1（Endothelin-1） Basic information
- Product Name:
- ET-1（Endothelin-1）
- Synonyms:
-
- ET-1（Endothelin-1）
- Endothelin-1 （ET-1）
- MW:
- 0
- Mol File:
- Mol File
ET-1（Endothelin-1） Usage And Synthesis
Mechanism of action
Endothelin-1 (ET-1) is a 21-amino-acid peptide that is produced by the vascular endothelium.It is a very potent vasoconstrictor that binds to VSM endothelin receptors ETA and ETB.The ET-1 receptors are linked to the Gq protein and IP3 signal transduction pathway. Therefore, ET-1 causes sarcoplasmic reticulum release of calcium, increasing the VSM contractility. Vascular endothelial cells secrete the majority of ET-1. The endothelins bind to two receptor subtypes: ETA, and ETB. In vascular tissue, ETA is located predominantly on smooth muscle cells, whereas ET B is found on both endothelial and smooth muscle cells.Activation of ETA by ET-1 leads to potent vasoconstriction from an increase in cytosolic calcium levels via influx of extracellular calcium and release from intracellular stores.The actions of ET B are more complicated.Like ETA, ET-1 activation of ETB on VSM cells leads to vasoconstriction. Furthermore, some studies suggest that in the pulmonary hypertensive state, blockade of both ETA and ETB is necessary to achieve maximal vasodilation. Activation of ET-B by ET-1 stimulates cyclooxygenase (COX) which catalyzes the formation of prostacyclin from arachidonic acid. Prostacyclin then binds to and activates the isoprostanoid receptor (IP) on VSM. ET-1 also activates ET-B which stimulates endothelial nitric oxide synthease (eNOS) to produce NO from L-arginine. Both prostacyclin and NO are potent vasodilators of VSM (relaxation). Additionally, ET-1 binds to the ETB receptors on the endothelium of pulmonary smooth muscle and stimulate the formation of NO, which produces vasodilation in the absence of smooth muscle ETA and ETB receptor activation.This receptor distribution helps to explain the phenomenon that ET -1 administration causes transient vasodilation (initial endothelial ETB activation) and hypotension, followed by prolonged vasoconstriction (smooth muscle ETA and ETB activation) and hypertension.