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International conference on endothelin
September 10, 2009One of the most intriguing developments in recent medical science is the discovery of the human chemical endothelin (ET). Since its detection in 1988, over 22,000 scholarly articles (about 3 per day) have been published on the subject, a new class of drugs has been developed, and 25 Phase I, II and III clinical trails are now underway. As the scientific and medical communities involved in ET move towards 25 years of understanding the protein, which future developments hold potential? At what risk? Do medicinal compounds look promising?
Donald Kohan, Professor of Medicine in the Division of Nephrology at the University of Utah Sciences Center and a leading global expert on endothelins is addressing these and other issues at the 11th International Conference on Endothelin being held September 9-12, 2009 in Montreal, CN. Dr. Kohan's invited presentation, "Clinical Relevance of ET Antagonist: An Update," is part of the program being sponsored by the American Physiological Society (APS; www.the-aps.org). A copy of the complete program is at http://the-aps.org/meetings/aps/ET11Montreal/index.htm.
What is Endothelin?
Identified in 1988, ET is produced by most tissues in the body. The protein is highly concentrated in the brain, lungs, kidney, heart, blood vessels and even in some cancer cells. ET is also the most potent vasoconstrictor (causing the blood vessels to constrict) known. It plays a major role in embryonic development and disease.
ET binds to two different types of receptors: endothelin A (ETR-A) and endothelin B (ETR-B). When ET connects with its receptors they react in different ways and have different impacts on disease.
The activated ETR-A receptor sends a signal to the blood vessels to contract, which then increases blood pressure. Conversely, when the ETR-B receptor is activated it signals the blood vessels to expand, thereby leading to a decrease in blood pressure.
ET can play a role in health and disease. In health, ET can regulate blood pressure and assist in normal cell growth. However, excessive ET production can lead to kidney, blood vessel, lung and heart disease. In addition, because ET can act as a growth factor through activation of ETR-A, ETR-A blockade may inhibit tumor growth or prevent cancer from metastasizing.
A New Class of Drugs: Endothelin Blockers
In an attempt to reduce the deleterious effects of ET, scientists have recently developed a new class of drugs. The drugs, known as ET receptor antagonists, bind to the ET receptors and block ET actions. Since the U.S. Food and Drug Administration (FDA) approved the first ET receptor antagonist drug in 2001 (for pulmonary hypertension), two additional related compounds have been approved.. These drugs block either ETR-A alone or both ETR-A and ETR-B receptors. Most recently, the FDA approved a combined ET receptor blocker for the treatment of scleroderma, a disease complicated by ulcers on fingers and toes.
"Endothelin Antagonists Present Great Promise"
"Endothelin antagonists present great promise," according to Dr. Kohan. To support his view, Kohan points out that studies being conducted in animals and humans suggest that there is a role for targeting ET receptors in kidney disease, difficult to treat high blood pressure, pulmonary hypertension and other disorders. In addition, studies in animals suggest that ET blockers may be of benefit in traumatic brain injury, eye disease and other conditions.
At the same time there are challenges. One challenge is how best to determine which diseases should be treated by targeting A receptors or the A and B receptors combined. Researchers do not currently have a full understanding of how ET receptors always interact with one another. Another consideration is drug side effects. "Studies need to be conducted on ET receptor antagonist-associated toxicity, especially as it relates to possible testicular toxicity, hepatic dysfunction and fluid retention," Kohan says. He also noted that ET receptor blockers should never be taken by pregnant women since ET aids fetal development.
Despite the challenges Kohan believes therapy with ET receptor antagonists hold great promise. After 21 years of examining the protein, Kohan says many scientists and physicians believe that ET is a rich target for the development of new receptor antagonist drugs. Says Kohan, "The antagonists are now clinically approved to treat a few diseases and we look forward to their being of substantial benefit in many more diseases."
American Physiological Society (APS)
Identified in 1988, ET is produced by most tissues in the body. The protein is highly concentrated in the brain, lungs, kidney, heart, blood vessels and even in some cancer cells. ET is also the most potent vasoconstrictor (causing the blood vessels to constrict) known. It plays a major role in embryonic development and disease.
ET binds to two different types of receptors: endothelin A (ETR-A) and endothelin B (ETR-B). When ET connects with its receptors they react in different ways and have different impacts on disease.
The activated ETR-A receptor sends a signal to the blood vessels to contract, which then increases blood pressure. Conversely, when the ETR-B receptor is activated it signals the blood vessels to expand, thereby leading to a decrease in blood pressure.
ET can play a role in health and disease. In health, ET can regulate blood pressure and assist in normal cell growth. However, excessive ET production can lead to kidney, blood vessel, lung and heart disease. In addition, because ET can act as a growth factor through activation of ETR-A, ETR-A blockade may inhibit tumor growth or prevent cancer from metastasizing.
A New Class of Drugs: Endothelin Blockers
In an attempt to reduce the deleterious effects of ET, scientists have recently developed a new class of drugs. The drugs, known as ET receptor antagonists, bind to the ET receptors and block ET actions. Since the U.S. Food and Drug Administration (FDA) approved the first ET receptor antagonist drug in 2001 (for pulmonary hypertension), two additional related compounds have been approved.. These drugs block either ETR-A alone or both ETR-A and ETR-B receptors. Most recently, the FDA approved a combined ET receptor blocker for the treatment of scleroderma, a disease complicated by ulcers on fingers and toes.
"Endothelin Antagonists Present Great Promise"
"Endothelin antagonists present great promise," according to Dr. Kohan. To support his view, Kohan points out that studies being conducted in animals and humans suggest that there is a role for targeting ET receptors in kidney disease, difficult to treat high blood pressure, pulmonary hypertension and other disorders. In addition, studies in animals suggest that ET blockers may be of benefit in traumatic brain injury, eye disease and other conditions.
At the same time there are challenges. One challenge is how best to determine which diseases should be treated by targeting A receptors or the A and B receptors combined. Researchers do not currently have a full understanding of how ET receptors always interact with one another. Another consideration is drug side effects. "Studies need to be conducted on ET receptor antagonist-associated toxicity, especially as it relates to possible testicular toxicity, hepatic dysfunction and fluid retention," Kohan says. He also noted that ET receptor blockers should never be taken by pregnant women since ET aids fetal development.
Despite the challenges Kohan believes therapy with ET receptor antagonists hold great promise. After 21 years of examining the protein, Kohan says many scientists and physicians believe that ET is a rich target for the development of new receptor antagonist drugs. Says Kohan, "The antagonists are now clinically approved to treat a few diseases and we look forward to their being of substantial benefit in many more diseases."
American Physiological Society (APS)
Endothelin Current Events and Endothelin News RSSKey player identified in cascade that leads to hypertension-related kidney damage
A key player in a cascade that likely begins with stress and leads to high blood pressure and kidney damage has been identified by researchers who say the finding may lead to better ways to control both.
Endothelin-1 inhibitors in chronic pancreatitis
Fibrosis is a key feature of chronic pancreatitis and pancreatic cancer. The extensive deposition of extracellular matrix proteins fosters the development of an exocrine and endocrine organ insufficiency, and accelerates progression of the tumour.
Males May Experience Greater Physical Pain Due To Lower Levels Of A Key Protein, Endothelin
Agonizing physical pain, known as vaso-occlusive pain, can afflict children who have sickle cell disease (SCD).
Endothelin-Related Drugs Benefit Patients With Pulmonary Hypertension
Recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of pulmonary arterial hypertension and provides hope for treating other chronic diseases.
Arterial, venous or total mesenteric ischemia/reperfusion causes different types of injury?
It is known that I/R induces an inflammatory response deleterious to the organ involved but also to the system as a whole.
Blood flow in Alzheimer's disease
Researchers have discovered that the enzyme, endothelin converting enzyme-2 (ECE-2), may cause the decrease in blood flow in the brain seen in Alzheimer's disease and contribute to progression of the disease.
Will IVF work for a particular patient? The answer may be found in her blood
For the first time, researchers have been able to identify genetic predictors of the potential success or failure of IVF treatment in blood.
Researchers may have found why women have an edge on salt-sensitive hypertension
Researchers may have found why women have an edge in keeping a healthier balance between the amount of salt they eat and excrete - at least before reaching menopause.
Mechanisms of cardiovascular disease and cancer give clues to new therapies
Cardiovascular conditions leading to heart attacks and strokes are treated quite separately from common cancers of the prostate, breast or lung, but now turn out to involve some of the same critical mechanisms at the molecular level.
Study shows pine bark naturally reduces cardiovascular risk factors in diabetics
A new study published in the May 2008 (volume 8, issue 25) edition of the journal of Nutrition Research shows Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, reduces blood sugar in type II diabetes patients, allows people to lower their antihypertensive medication and improves cardiovascular disease (CVD) risk factors.
More Endothelin Current Events and Endothelin News Articles
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Endothelin Protocols (Methods in Molecular Biology, 206) (Methods in Molecular Biology) by Janet J. Maguire (Editor), Anthony P. Davenport (Editor) A panel of multidisciplinary experts describes in detail readily reproducible methods to investigate all aspects of the endothelin system from its synthesis and metabolism, to its function in health and disease. Theses methods use state-of-the-art molecular techniques to quantify the expression of mRNA for both endothelin receptors and the endothelin converting enzymes. They show how peptides, precursors, receptors, and synthetic enzymes can be localized and quantified in plasma, culture supernatants, tissue homogenate, and tissue sections using antibodies. Several in vivo protocols illustrate the role of the endothelin peptides in healthy human individuals and describe animal models that can be used to predict the therapeutic potential of cardiovascular drugs that manipulate... |
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Endothelin Receptors: From the Gene to the Human (Pharmacology and Toxicology) by Robert R. Ruffolo (Editor) Since the discovery of endothelin, major advances have been made in understanding the molecular structure and function of the endothelin receptors. At least two subtypes of receptors, designated ETA and ETB, have been identified through biochemical and pharmacological techniques. These subtypes are cloned and expressed and additional subtypes appear to exist. The biochemical events involved in the signal transduction processes that ultimately activate the cellular machinery involved in the end-organ responses are presented, as are the mechanisms by which the receptors recognize specific and different G-proteins. Functions mediated by the receptors at the cellular, tissue and, organ level are reviewed in detail, as well as the roles that they may play a part in the physiologic and... |
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Endothelin: Tole in Health & by GULATI (Author) Endothelin summarizes the progress made in the field of endothelin research since its discovery. Initially it was believed to have vasoactive properties, however it is now known that endothelin, as well as vasculature, is involved in many other systems. Care has been taken to include almost all major systems into the text. The book focuses on the role of endothelin in the pathophysiology of several diseases, both cardiovascular and non-cardiovascular, and its role in inflammation. Endothelin interaction with a variety of other regulatory agents is discussed, providing a text which will be of great value to scientists engaged in studies on this multifunctional polypeptide. |
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Endothelins in Biology and Medicine by John P. Huggins (Author), John T. Pelton (Author) Endothelin-1 (ET-1), a peptide discovered in 1988, is one of the most potent contractors of vascular smooth muscle. Since their discovery, ETs have generated enormous interest in the scientific and pharmaceutical communities, prompting extensive research. This book addresses the latest findings regarding ETs-how they function, their effects, and characteristics. Divided into five sections, the book covers: endothelin receptors, endothelin synthesis and degradation, endothelin pathophysiology, ligand structure and activity relationships, and clinical studies. Pharmacologists, toxicologists, and pharmaceutical researchers will all benefit from this thorough review of current findings and future directions in ET research. |
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Endothelin Receptors and Signaling Mechanisms (Biotechnology Intelligence Unit) by David M. Pollock (Editor), Robert F. Highsmith (Editor) This book focuses on the wide variety of intracellular events that occur as a result of endothelin receptor activation. This includes a discussion of the various pathways by which endothelin activates Ca2+ signals from several intra- and extracellular sources and the effects of endothelin on ion channels and membrane function. In addition, the mechanisms by which endothelin influences the ion transport within the renal epithelium are covered, as well as the signal transduction pathways activated by endothelin in both cardiac tissue and vascular smooth muscle. |
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Endothelin (Clinical Physiology Series) by Gabor M. Rubanyi (Editor) Merely three years after the discovery of endothelin, a large amount of information has been generated about the molecular biology, biosynthesis, biological actions and potential physiological and pathological importance of this unique peptide and its isoforms. This first book on endothelins summarizes the early events which lead to the discovery of endothelin, the progress made in understanding the peptide's physiological role, and the current state-of-the-art in contemporary endothelin research. The book also discusses the potential significance of endothelins in health and disease, covers the potential role of the peptides in the integrated control of the cardiovascular system, and outlines future research directions. This comprehensive monograph is an indispensable reference for basic... | |
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Endothelin: Webster's Timeline History, 1988 - 2007 by Icon Group International (Author) Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Endothelin," including when used in literature (e.g. all authors that might have Endothelin in their name). As such, this book represents the largest compilation of timeline events associated with Endothelin when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts, social sciences... |
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Endothelins: Webster's Facts and Phrases by Icon Group International (Author) Ever need a fact or quotation on "endothelins"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "endothelins," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "endothelins," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book... |
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Einfluß von Endothelin-1 auf Kontraktionskraftentwicklung und intrazelluläre Calcium-Homöostase des Myokards by Matthias Zirnig (Author) |
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Pulmonary Actions of the Endothelins (Respiratory Pharmacology and Pharmacotherapy) by Goldie (Editor), Hay (Editor) This book addresses the subject of the biology of the endothelin peptides in the lung, with particular reference to the respiratory tract and the possible mediator roles of these peptides in lung disease. The book provides an up-to-date analysis of the current literature concerning the actions of the endothelins in the lung. Specific chapters are devoted to our current understanding of endothelin synthesis, receptor subtype activation, distribution and density in the airways, its actions in vascular and airway smooth muscle and nerves and its role in tissue development, differentiation and disease. This volume will be of interest to both nonclinical and clinical researchers in pulmonary biology, as well as to teachers in academic disciplines targetting aspects of lung function and... |
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