Endothelin Family Related Drug Discovery Products
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Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The endogenous endothelin (ET) peptides play a variety of roles in pain-related processes. Endothelin receptor antagonists can be applied locally to treat pain that is aggravated by conditions like inflammation, skin wounds, cancer, sickle cell crises, and medications that imitate neuropathic and inflammatory pain. Many of the effects of endogenously produced endothelin are mimicked by an acute, local subcutaneous dosage of endothelin. At low concentrations, endothelin increases the sensitivity of nocifensive reactions to mechanical, thermal, and chemical stimuli while also producing pain at very high doses.
Creative Biolabs offers high-quality assays and products to help research groups accelerate drug discovery of endothelin family:
Overview of Endothelin Family
The human kidney expresses all three endothelin (ET) family peptides, ET-1, ET-2, and ET-3, although ET-1 is the major isoform. While ET-3 has limited affinity for the ETA receptor at normal concentrations, ET-1 and ET-2 bind to two G-protein-coupled receptors, ETA and ETB. The class A G-protein-coupled receptors, which include the endothelin receptors, are a class of proteins that have been successfully used as drug development targets.
Fig.1 Model of the ET-1 signaling pathway in the renal vasculature. (Maguire & Davenport, 2015)
Endothelin-1 preferentially activates the ETA receptor while endothelin-3 does not. The aorta, heart, and kidney have the highest levels of ETA receptor messenger RNA expression, but not endothelial cells, indicating that smooth muscle cells are the only cells in the vascular system that express this receptor.
Both endothelin-1 and endothelin-3 activate the ETB receptor. In cultivated endothelium cells, messenger RNA for the ETB receptor is most strongly expressed. Nitric oxide and prostaglandins are two examples of the vasodilator chemicals that are produced when this endothelial cell ETB receptor is activated. Moreover, vascular smooth muscle has been found to have messenger RNA for the ETB receptor, suggesting that this RNA may mediate vasoconstriction. The ETB is preferentially activated over the ETA receptor by a number of agonists.
Endothelin Family Drug Discovery
While normal physiological pain is unaffected, endothelin-1 and its receptors are linked to a variety of long-lasting, increased pain conditions that result from inflammation, injury, and illnesses that impact peripheral tissues. This "endothelin axis" appears to affect a wide range of ion channels and transmitter pathways, suggesting that diverging signaling pathways like MAPKs are responsible for these extensive effects. Early therapeutic outcomes, such as in the treatment of cancer pain, support the continued research and development of medications that target endothelin receptors to prevent or treat severe pain.
Reference
- Maguire, J. J., & Davenport, A. P. Endothelin receptors and their antagonists. In Seminars in nephrology. 2015, 35(2): 125-136.
