Endothelin receptor antagonists: a brief review

1994 ◽  
Vol 72 (11) ◽  
pp. 1469-1471 ◽  
Author(s):  
Suzanne Moreland
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Receptor Subtypes ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Vascular Activity ◽  
Vasodilatory Activity ◽  
Healthy Control ◽  
Circulating Levels

The endothelins are a family of potent vasoconstrictors, some of which also have vasodilatory activity. In many diseases associated with tissue hypoxia or ischemia and in diseases in which vasoconstriction plays a role, the circulating levels of endothelin are higher than in healthy, control subjects. These findings stimulated research aimed at discovering endothelin receptor antagonists. This review focuses on the binding potency and vascular activity of these new peptide and nonpeptide endothelin receptor antagonists.Key words: endothelin, endothelin receptor subtypes, vascular smooth muscle, endothelin receptor antagonist.

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

scholarly journals The endothelin axis in cancer: the promise and the challenges of molecularly targeted therapyThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (8) ◽  
pp. 473-484 ◽  
Author(s):  
Anna Bagnato ◽  
Francesca Spinella ◽  
Laura Rosanò
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Molecular Level ◽  
Receptor Subtypes ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Mesenchymal Transition ◽  
Novel Therapeutic Strategies ◽  
G Protein Coupled ◽  
Selection Of

The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and 2 G protein-coupled receptor subtypes, ETAR and ETBR, promotes growth and progression of a variety of tumors, such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast, lung, bladder, endometrial carcinoma, Kaposi’s sarcoma, brain tumors, and melanoma. Acting on selective receptors, ET-1 regulates mitogenesis, cell survival, angiogenesis, bone remodeling, stimulation of nociceptors, tumor-infiltrating immune cells, epithelial-to-mesenchymal transition, invasion, and metastatic dissemination. At the molecular level, endothelin receptor antagonists, besides providing ideal tools for dissecting the ET axis, have demonstrated their potential in developing novel therapeutic strategies. Emerging experimental and clinical data demonstrate that interfering with endothelin receptors provides an opportunity for the development of rational combinatorial approaches using endothelin receptor antagonists in combination with chemotherapy or molecularly targeted therapy.

scholarly journals Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease

2009 ◽  
Vol 297 (1) ◽  
pp. G27-G33 ◽  
Author(s):  
Hong-Qiang Feng ◽  
Nate D. Weymouth ◽  
Don C. Rockey
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Receptor Antagonist ◽  
Intravenous Infusion ◽  
Biological Effects ◽  
Portal Pressure ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Receptor Antagonism

Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage with carbon tetrachloride (CCl4). Portal pressure was recorded acutely during intravenous infusion of endothelin receptor antagonists in normal or portal hypertensive mice. In vivo microscopy was used to monitor sinusoidal dynamics. Additionally, the effect of chronic exposure to endothelin antagonists was assessed in mice during induction of fibrosis and cirrhosis with CCl4 for 8 wk. Intravenous infusion of ET-A receptor antagonists into normal and cirrhotic mice reduced portal pressure whereas ET-B receptor antagonism increased portal pressure. A mixed endothelin receptor antagonist also significantly reduced portal pressure. Additionally, the ET-A receptor antagonist caused sinusoidal dilation, whereas the ET-B receptor antagonist caused sinusoidal constriction. Chronic administration of each the endothelin receptor antagonists during the induction of fibrosis and portal hypertension led to reduced fibrosis, a significant reduction in portal pressure, and altered sinusoidal dynamics relative to controls. Acute effects of endothelin receptor antagonists are likely directly on the hepatic and sinusoidal vasculature, whereas chronic endothelin receptor antagonism appears to be more complicated, likely affecting fibrogenesis and the hepatic microcirculation. The data imply a relationship between hepatic fibrogenesis or fibrosis and vasomotor responses.

ChemInform Abstract: 2-Aryloxycarbonylthiophene-3-sulfonamides: Highly Potent and ETA Selective Endothelin Receptor Antagonists.

ChemInform ◽  
2010 ◽  
Vol 28 (50) ◽  
pp. no-no
Author(s):  
B. RAJU ◽  
C. WU ◽  
R. CASTILLO ◽  
I. OKUN ◽  
F. STAVROS ◽  
...  
Keyword(s):  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists
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