A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.
Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.
A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.
21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.
A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)
A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63)
A 21-amino acid peptide produced predominantly within the kidney and intestine, with smaller amounts produced in the myocardium, placenta, and uterus, but the cells of origin are not clear. Endothelin-2 has no unique physiologic functions, as compared with endothelin-1. (N Eng J Med 1995;333(6):356-63)
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Venoms from SNAKES of the viperid family. They tend to be less toxic than elapid or hydrophid venoms and act mainly on the vascular system, interfering with coagulation and capillary membrane integrity and are highly cytotoxic. They contain large amounts of several enzymes, other factors, and some toxins.
A group of compounds that contain the structure SO2NH2.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Seven membered heterocyclic rings containing a NITROGEN atom.
Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES.
Peptides composed of between two and twelve amino acids.
Drugs used to cause constriction of the blood vessels.
A family of hexahydropyridines.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
The nonstriated involuntary muscle tissue of blood vessels.
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The circulation of the BLOOD through the vessels of the KIDNEY.
The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).
Compounds that contain a 1-dimethylaminonaphthalene-5-sulfonyl group.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Drugs used to cause dilation of the blood vessels.
The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.
Arteries which arise from the abdominal aorta and distribute to most of the intestines.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
The veins and arteries of the HEART.
A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.
Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.
The main trunk of the systemic arteries.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The smallest divisions of the arteries located between the muscular arteries and the capillaries.
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.
The flow of BLOOD through or around an organ or region of the body.
A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.
Elements of limited time intervals, contributing to particular results or situations.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The internal portion of the kidney, consisting of striated conical masses, the renal pyramids, whose bases are adjacent to the cortex and whose apices form prominent papillae projecting into the lumen of the minor calyces.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
The neural systems which act on VASCULAR SMOOTH MUSCLE to control blood vessel diameter. The major neural control is through the sympathetic nervous system.
The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.
The circulation of the BLOOD through the LUNGS.
A competitive inhibitor of nitric oxide synthetase.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
The vessels carrying blood away from the heart.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
Part of the arm in humans and primates extending from the ELBOW to the WRIST.
Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome).
Treatment process involving the injection of fluid into an organ or tissue.
An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.
A nonsteroidal abortifacient agent that is effective in both the first and second trimesters of PREGNANCY.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
An increase in the excretion of URINE. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
Relatively complete absence of oxygen in one or more tissues.
The circulation of the BLOOD through the MICROVASCULAR NETWORK.
The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.
Sodium chloride used in foods.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
Sodium excretion by URINATION.
The hollow, muscular organ that maintains the circulation of the blood.
A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
The number of times the HEART VENTRICLES contract per unit of time, usually per minute.
The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries.
A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.
An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
A region, of SOMITE development period, that contains a number of paired arches, each with a mesodermal core lined by ectoderm and endoderm on the two sides. In lower aquatic vertebrates, branchial arches develop into GILLS. In higher vertebrates, the arches forms outpouchings and develop into structures of the head and neck. Separating the arches are the branchial clefts or grooves.
A syndrome characterized by the clinical triad of advanced chronic liver disease, pulmonary vascular dilatations, and reduced arterial oxygenation (HYPOXEMIA) in the absence of intrinsic cardiopulmonary disease. This syndrome is common in the patients with LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL).
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Contractile activity of the MYOCARDIUM.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.
A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment.
Regional infusion of drugs via an arterial catheter. Often a pump is used to impel the drug through the catheter. Used in therapy of cancer, upper gastrointestinal hemorrhage, infection, and peripheral vascular disease.
The rate dynamics in chemical or physical systems.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)
Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.
The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.
The circulation of blood through the CORONARY VESSELS of the HEART.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A method of non-invasive, continuous measurement of MICROCIRCULATION. The technique is based on the values of the DOPPLER EFFECT of low-power laser light scattered randomly by static structures and moving tissue particulates.
A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function.
A condition associated with VENTRICULAR SEPTAL DEFECT and other congenital heart defects that allow the mixing of pulmonary and systemic circulation, increase blood flow into the lung, and subsequent responses to low oxygen in blood. This complex is characterized by progressive PULMONARY HYPERTENSION; HYPERTROPHY of the RIGHT VENTRICLE; CYANOSIS; and ERYTHROCYTOSIS.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
An essential amino acid that is physiologically active in the L-form.
The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.
An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. (1/1687)

The terminal colon is aganglionic in mice lacking endothelin-3 or its receptor, endothelin B. To analyze the effects of endothelin-3/endothelin B on the differentiation of enteric neurons, E11-13 mouse gut was dissociated, and positive and negative immunoselection with antibodies to p75(NTR )were used to isolate neural crest- and non-crest-derived cells. mRNA encoding endothelin B was present in both the crest-and non-crest-derived cells, but that encoding preproendothelin-3 was detected only in the non-crest-derived population. The crest- and non-crest-derived cells were exposed in vitro to endothelin-3, IRL 1620 (an endothelin B agonist), and/or BQ 788 (an endothelin B antagonist). Neurons and glia developed only in cultures of crest-derived cells, and did so even when endothelin-3 was absent and BQ 788 was present. Endothelin-3 inhibited neuronal development, an effect that was mimicked by IRL 1620 and blocked by BQ 788. Endothelin-3 failed to stimulate the incorporation of [3H]thymidine or bromodeoxyuridine. Smooth muscle development in non-crest-derived cell cultures was promoted by endothelin-3 and inhibited by BQ 788. In contrast, transcription of laminin alpha1, a smooth muscle-derived promoter of neuronal development, was inhibited by endothelin-3, but promoted by BQ 788. Neurons did not develop in explants of the terminal bowel of E12 ls/ls (endothelin-3-deficient) mice, but could be induced to do so by endothelin-3 if a source of neural precursors was present. We suggest that endothelin-3/endothelin B normally prevents the premature differentiation of crest-derived precursors migrating to and within the fetal bowel, enabling the precursor population to persist long enough to finish colonizing the bowel.  (+info)

Different contributions of endothelin-A and endothelin-B receptors in the pathogenesis of deoxycorticosterone acetate-salt-induced hypertension in rats. (2/1687)

We investigated the involvement of actions mediated by endothelin-A (ETA) and endothelin-B (ETB) receptors in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertension in rats. Two weeks after the start of DOCA-salt treatment, rats were given ABT-627 (10 [mg/kg]/d), a selective ETA receptor antagonist; A-192621 (30 [mg/kg]/d), a selective ETB receptor antagonist; or their vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Treatment with DOCA and salt for 2 weeks led to a mild but significant hypertension; in vehicle-treated DOCA-salt rats, systolic blood pressure increased markedly after 3 to 4 weeks. Daily administration of ABT-627 for 2 weeks almost abolished any further increases in blood pressure, whereas A-192621 did not affect the development of DOCA-salt-induced hypertension. When the degree of vascular hypertrophy of the aorta was histochemically evaluated at 4 weeks, there were significant increases in wall thickness, wall area, and wall-to-lumen ratio in vehicle-treated DOCA-salt rats compared with uninephrectomized control rats. The development of vascular hypertrophy was markedly suppressed by ABT-627. In contrast, treatment with A-192621 significantly exaggerated these vascular changes. In vehicle-treated DOCA-salt rats, renal blood flow and creatinine clearance decreased, and urinary excretion of protein, blood urea nitrogen, fractional excretion of sodium, and urinary N-acetyl-beta-glucosaminidase activity increased. Such damage was overcome by treatment with ABT-627 but not with A-192621; indeed, the latter agent led to worsening of the renal dysfunction. Histopathologic examination of the kidney in vehicle-treated DOCA-salt rats revealed tubular dilatation and atrophy as well as thickening of small arteries. Such damage was reduced in animals given ABT-627, whereas more severe histopathologic changes were observed in A-192621-treated animals. These results strongly support the view that ETA receptor-mediated action plays an important role in the pathogenesis of DOCA-salt-induced hypertension. On the other hand, it seems likely that the ETB receptor-mediated action protects against vascular and renal injuries in this model of hypertension. A selective ETA receptor antagonist is likely to be useful for treatment of subjects with mineralocorticoid-dependent hypertension, whereas ETB-selective antagonism alone is detrimental to such cases.  (+info)

Endogenous endothelin-1 depresses left ventricular systolic and diastolic performance in congestive heart failure. (3/1687)

Endothelin-1 (ET-1) is a positive inotrope in normal hearts; however, the direct cardiac effects of endogenous ET-1 in congestive heart failure (CHF) are unknown. We evaluated the cardiac responses to endogenous ET-1 using an ETA and ETB receptor blocker (L-754,142) in seven conscious dogs before and after pacing-induced CHF. Before CHF, when the plasma ET-1 was 7.3 +/- 1.7 fmol/ml, L-754,142 caused no significant alterations in heart rate, left ventricular (LV) end-systolic pressure, total systemic resistance, and the time constant of LV relaxation (tau). LV contractile performance, measured by the slopes of LV pressure (P)-volume (V) relation (EES), dP/dtmax-end-diastolic V relation (dE/dtmax), and stroke work-end-diastolic V relation, was also unaffected. After CHF, when the plasma ET-1 was significantly increased to 14.1 +/- 3.0 fmol/ml (p <.05), L-754,142 produced a significant decreases in LV end-systolic pressure (101 +/- 11 versus 93 +/- 8 mm Hg) and total systemic resistance (0.084 +/- 0.022 versus 0.065 +/- 0.15 mm Hg/ml/min). The tau (42 +/- 12 versus 38 +/- 10 ms), mean left atrial P (22 +/- 5 versus 18 +/- 4 mm Hg) (p <.05), and minimum LVP were also significantly decreased. After CHF, the slopes of P-V relations, EES (3.4 +/- 0.4 versus 4.8 +/- 0.8 mm Hg/ml), dE/dtmax (42.4 +/- 7.8 versus 50.0 +/- 7.8 mm Hg/s/ml), and stroke work-end-diastolic V relation (58.1 +/- 3.3 versus 72.4 +/- 5.2 mm Hg) (p <.05) all increased after L-754,142, indicating enhanced contractility. Before CHF, low levels of endogenous ET-1 have little cardiac effect. However, after CHF, elevated endogenous ET-1 produces arterial vasoconstriction, slows LV relaxation, and depresses LV contractile performance. Thus, elevated endogenous ET-1 may contribute to the functional impairment in CHF in this canine model.  (+info)

Transcriptional down-regulation of the rabbit pulmonary artery endothelin B receptor during phenotypic modulation. (4/1687)

1. We confirmed that endothelium-independent contraction of the rabbit pulmonary artery (RPA) is mediated through both an endothelin A (ET(A)R) and endothelin B (ET(B2)R) receptor. 2. The response of endothelium-denuded RPA rings to endothelin-1 (ET-1, pD2 = 7.84 +/- 0.03) was only partially inhibited by BQ123 (10 microM), an ET(A)R antagonist. 3. Pretreatment with 1 nM sarafotoxin S6c (S6c), an ET(B)R agonist, desensitized the ET(B2)R and significantly attenuated the response to ET-3 (pD2 = 7.40 +/- 0.02 before, <6.50 after S6c). 4. Pretreatment with S6c had little effect on the response to ET-1, but BQ123 (10 microM) caused a parallel shift to the right of the residual ETAR-mediated response to ET-1 (pD2 = 7.84 +/- 0.03 before S6c, 7.93 +/- 0.03 after S6c, 6.81 +/- 0.05 after BQ123). 5. Binding of radiolabelled ET-1 to early passage cultures of RPA vascular smooth muscle cells (VSMC) displayed two patterns of competitive displacement characteristic of the ET(A)R (BQ123 pIC50 = 8.73 +/- 0.05) or ET(B2)R (S6c pIC50 = 10.15). 6. Competitive displacement experiments using membranes from late passage VSMC confirmed only the presence of the ET(A)R (ET-1 pIC50 = 9.3, BQ123 pIC50 = 8.0, S6c pIC50 < 6.0). 7. The ET(A)R was functionally active and coupled to rises in intracellular calcium which exhibited prolonged homologous desensitization. 8. Using a reverse transcriptase polymerase chain reaction for the rabbit ET(B2)R, we demonstrated the absence of mRNA expression in phenotypically modified VSMC. 9. We conclude that the ET(B2)R expressed by VSMC which mediates contraction of RPA is rapidly down-regulated at the transcriptional level during phenotypic modulation in vitro.  (+info)

Effects of tumour necrosis factor-alpha on left ventricular function in the rat isolated perfused heart: possible mechanisms for a decline in cardiac function. (5/1687)

1. The cardiac depressant actions of TNF were investigated in the isolated perfused rat heart under constant flow (10 ml min(-1)) and constant pressure (70 mmHg) conditions, using a recirculating (50 ml) mode of perfusion. 2. Under constant flow conditions TNF (20 ng ml(-1)) caused an early (< 25 min) decrease in left ventricular developed pressure (LVDP), which was maintained for 90 min (LVDP after 90 min: control vs TNF; 110 +/- 4 vs 82 +/- 10 mmHg, P < 0.01). 3. The depression in cardiac function seen with TNF under constant flow conditions, was blocked by the ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, (LVDP after 90 min: TNF vs TNF with NOE; 82 +/- 10 vs 11 +/- 5 mmHg, P < 0.05). 4. In hearts perfused at constant pressure, TNF caused a decrease in coronary flow rate (change in flow 20 min after TNF: control vs TNF; -3.0 +/- 0.9 vs -8.7 +/- 1.2 ml min(-1), P < 0.01). This was paralleled by a negative inotropic effect (change in LVDP 20 min after TNF: control vs TNF; -17 +/- 7 vs -46 +/- 6 mmHg, P < 0.01). The decline in function was more rapid and more severe than that seen under conditions of constant flow. 5. These data indicate that cardiac function can be disrupted by TNF on two levels, firstly via a direct, ceramidase dependant negative inotropic effect, and secondly via an indirect coronary vasoconstriction.  (+info)

Nucleotide sequence of endothelin-B receptor gene reveals origin of piebald mutation in laboratory mouse. (6/1687)

Piebald (Ednrbs) is a coat color mutation of laboratory mice caused by a decreased expression of endothelin-B receptor gene (Ednrb). The IITES and JF1 mouse strains, whose origins are believed to be different from those of the common laboratory inbred strains, also show a phenotype similar to Ednrbs. In the present study, we found that the nucleotide sequence of the Ednrb gene of the IITES and JF1 mice is identical to that of the Ednrbs allele, Ednrbs allele has an RFLP of the Ednrb gene identical with that of M. m. molossinus but different from other subspecies, and at least particular regions of chromosome 14 proximal to the Ednrb locus of the IITES and JF1 strains are derived from M. m. molossinus. These findings clearly indicate that the Ednrbs allele of the laboratory mice has its origin in M. m. molossinus.  (+info)

Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. (7/1687)

BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of +info)

Maintenance of blood pressure in normotensive dogs by endothelin. (8/1687)

The role of endothelin (ET)-1 in blood pressure homeostasis and the interaction with the renin-angiotensin system (RAS) was investigated in normotensive conscious dogs. ETA receptors were blocked by LU-135252 (1-30 mg/kg); trandolapril (2 mg/kg) or losartan (10 mg/kg) was used to inhibit the RAS. LU-135252 in oral doses of 3-30 mg/kg significantly reduced mean arterial pressure (MAP) by approximately 10 mmHg maximally, whereas trandolapril or losartan were without any effect. MAP reduction was more pronounced when LU-135252 was combined with either losartan (-15.5 +/- 3.2 mmHg; 2 h postadministration; P < 0.05) or trandolapril (-30.9 +/- 3.6 mmHg; P < 0.05). When endogenous nitric oxide (NO) generation was blocked but NO concomitantly infused, this synergistic effect on MAP was prevented. The data show that ET-1 contributes to the maintenance of blood pressure via ETA receptors. Furthermore, ET-1 and ANG II play a prominent role in the control of blood pressure by opposing the effects of NO. The pronounced blood pressure fall after combined blockade of ETA receptors and the RAS may be mediated by an enhanced release of NO.  (+info)

article{4ac00774-2f85-4776-9b6d-b14fe0384556, abstract = {Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. Endothelin ETB receptor antisense or mismatch oligodeoxynucleotides showed no alteration of the endothelin-1-induced contraction. Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors mediating contraction in the human superficial temporal artery.}, author = {Adner, Mikael and Erlinge, David and Salford, Leif and Yee, Frances and Wahlestedt, Claes and Edvinsson, Lars}, issn = ...
Tezosentan is a potent, specific, and highly water-soluble ET receptor antagonist. It binds with a high affinity to human ETA receptors. The lower inhibitory potency observed for the human ETA receptors expressed in baculovirus-infected insect cells compared with CHO cells is likely to be due to a different glycosylation pattern, a modified receptor conformation due to the marked overexpression, or an abnormal G protein coupling of the receptor in this expression system. The high-affinity binding of tezosentan on ETA receptors is also confirmed in functional assays. Tezosentan also has a high affinity for ETB receptors and is about 30-fold more potent on ETA receptors than on ETBreceptors. It is a competitive antagonist, and therefore its inhibitory activity will depend on the agonist concentration. It is a very specific antagonist for ET receptors.. The in vivo pharmacological properties of tezosentan have been evaluated by its inhibition of the pressor effect of big ET-1 and by the increase in ...
Plasma levels of ET-1 and its precursor, big ET-1, are strong independent predictors of death (16,35). Thus, ET antagonists are of great clinical interest as mortality remains high in patients with CHF in spite of currently available drugs. Endothelin-1 exerts its vasoconstrictive effects through activation of ETA and ETB receptors on vascular smooth muscle cells. The ETA receptor also mediates proliferation of vascular smooth muscle cells (9). In contrast, ETB receptors on endothelial cells mediate the release of vasodilating and antiproliferative NO and prostaglandins (10-12) and are involved in the clearance of ET-1 (22-25). Indeed, selective ETB antagonism exerts unfavorable hemodynamic effects (36,37). Therefore, there is particular interest in selective ETA receptor antagonists as therapeutic agents in chronic heart failure. As in previous studies with other ET-1 receptor antagonists, ET-1 plasma levels increased significantly after administration of the selective ETA receptor antagonist ...
TY - JOUR. T1 - Bosentan ameliorates cyclosporin A-induced hypertension in rats and primates. AU - Bartholomeusz, Briony. AU - Hardy, Kenneth J.. AU - Nelson, Angela S.. AU - Phillips, Paddy A.. PY - 1996/6/1. Y1 - 1996/6/1. N2 - Cyclosporine-induced hypertension is a major problem in transplant therapy. The pathophysiology of this disease is unclear. Cyclosporine increases endothelin synthesis and release, which may contribute to this hypertension. We examined the effects of chronic endothelin receptor blockade with the novel nonpeptide endothelin receptor antagonist bosentan in two animal models of cyclosporine-induced hypertension. Cyclosporine was administered daily to female Wistar rats (10 mg/kg per day SC for 30 days) and marmosets (30 mg/kg per day PP for 20 days). Control rats received vehicle. Tail-cuff systolic pressure was significantly elevated in the cyclosporine-treated animals before the last week of treatment. Bosentan (100 mg/kg) in arabic gum or arabic gum alone was given ...
Macitentan may be the lately approved dual endothelin-receptor antagonist (Period) for the treating symptomatic pulmonary arterial hypertension. hypertension sufferers with macitentan resulted in statistically significant improvements in useful class, workout tolerance, and hemodynamic variables, and a decrease in morbidity within an event-driven long-term trial. solid course=kwd-title Keywords: endothelin, endothelin receptor antagonists, macitentan, pulmonary arterial hypertension Pulmonary arterial hypertension Pulmonary arterial hypertension (PAH) is normally a intensifying and BRL-15572 supplier lethal disease seen as a remodeling from the pulmonary arterioles with consequent enhance from the pulmonary vascular level of resistance (PVR) with eventual best ventricular failing and ultimately loss of life. Furthermore, despite targeted remedies, the disease continues to be fatal.1 The organic history of PAH as well as the survival prices for patients experiencing this disease had been ...
TY - JOUR. T1 - Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method. AU - Han, Seong Gu. AU - Ko, Sanghwan. AU - Lee, Won Kyu. AU - Jung, Sang Taek. AU - Yu, Yeon Gyu. PY - 2017/12/1. Y1 - 2017/12/1. N2 - G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive. In this study, we have developed a novel strategy to investigate the precise ligand recognition mechanisms involved in the interaction of endothelin receptor type A (ETA) with its ...
Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.
Endothelin 1 may have a role in the development of acute airway narrowing in asthma. Blockade of the endothelin system may thereby protect against airway narrowing. Two receptors exist for endothelin 1, Endothelin A & B. Both can be blocked by Bosentan, and the A receptor by ambrisentan. Both medications are currently in use for the treatment of pulmonary arterial hypertension. The investigators will endeavour to examine the potential role of endothelin 1 in the development of airway narrowing in asthma through blockade of the endothelin receptors A&B through the use of bosentan and ambrisentan ...
This is the first study to investigate the effects of tezosentan, a non-selective endothelin receptor antagonist, in LPS challenged rats with cirrhosis. LPS was administered intravenously, followed by intravenous administration of tezosentan or placebo one hour later. Thus the study design mimics the occurrence of severe endotoxaemia by intravenous administration of a Gram negative bacterial product. In this study, normal rats were not investigated as we observed that 1 mg/kg LPS intravenously had only minor effects on serum transaminase activities and had no lethal effects (unpublished results, Moreau and Lebrec, 2001). Similar findings have been previously observed.6,7. In this series of rats with cirrhosis, LPS administration induced a significant decrease in arterial pressure and an increase in plasma endothelin levels associated with elevated serum transaminase activities and high mortality indicating endotoxin induced liver injury. These results were similar to those previously observed ...
INTRODUCTION: The purpose of this study was to determine whether prolonged oral therapy with sitaxsentan, a potent selective ET(A) endothelin receptor antagonist, normalizes systolic blood pressure in spontaneously hypertensive hamsters, a new rodent
At the cell surface, βARs and endothelin receptors can regulate nitric oxide (NO) production. β-adrenergic receptors (βARs) and type B endothelin receptors (ETB) are present in cardiac nuclear membranes and regulate transcription. The present study investigated the role of the NO pathway in the regulation of gene transcription by these nuclear G protein-coupled receptors. Nitric oxide production and transcription initiation were measured in nuclei isolated from the adult rat heart. The cell-permeable fluorescent dye 4,5-diaminofluorescein diacetate (DAF2 DA) was used to provide a direct assessment of nitric oxide release. Both isoproterenol and endothelin increased NO production in isolated nuclei. Furthermore, a β3AR-selective agonist, BRL 37344, increased NO synthesis whereas the β1AR-selective agonist xamoterol did not. Isoproterenol increased, whereas ET-1 reduced, de novo transcription. The NO synthase inhibitor l-NAME prevented isoproterenol from increasing either NO production or de ...
OBJECTIVE: Endothelins (ETs) are involved in several inflammatory events. The present study investigated the efficacy of bosentan, a dual ETA/ETB receptor antagonist, in collagen-induced arthritis (CIA) in mice. TREATMENT: CIA was induced in DBA/1J mice. Arthritic mice were treated with bosentan (100 mg/kg) once a day, starting from the day when arthritis was clinically detectable. METHODS: CIA progression was assessed by measurements of visual clinical score, paw swelling and hypernociception. Histological changes, neutrophil infiltration and pro-inflammatory cytokines were evaluated in the joints. Gene expression in the lymph nodes of arthritic mice was evaluated by microarray technology. PreproET-1 mRNA expression in the lymph nodes of mice and in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time PCR. The differences were evaluated by one-way ANOVA or Students t test. RESULTS: Oral treatment with bosentan markedly ameliorated the clinical aspects of CIA (visual clinical score,
TY - JOUR. T1 - Endothelin receptor alterations in equine airway hyperreactivity. AU - Venugopal, Changaram S.. AU - Polikepahad, Sumanth. AU - Holmes, Earnestine P.. AU - Vanden Heuvel, John Patrick. AU - Leas, Tara L.. AU - Moore, Rustin M.. PY - 2006/1/1. Y1 - 2006/1/1. N2 - The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). The right diaphragmatic lobe of the lung of 8 clinically healthy (unaffected) and 8 SPAOPD-affected horses was collected immediately after euthanasia. Bronchial rings (4 mm wide) were prepared and mounted in organ baths and attached to force transducers interfaced with a polygraph. Four rings were used to study each ET-1 receptor; 1 ring served as the control, and the other 3 were incubated with 10-9, 10-7, or 10-5 M of either BQ-123, an ETA-receptor antagonist, or IRL-1038, an ETB-receptor antagonist. Cumulative ...
Find Endothelin Receptors research area related information and Endothelin Receptors research products from R&D Systems. Learn more.
Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors
Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i.d. 5.5mm) and human radial (i.d. 3.23mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1-10µM), macitentan (0.03-0.3µM) or ambrisentan (0.1-1µM). RESULTS: All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in both arteries. The Clark plot and analysis gave the following pKB values: bosentan, pulmonary artery 6.28±0.13 and ...
Introduction. Endothelin-1 (ET-1), together with its cognate receptors endothelin receptor subtype A (ET-RA) and endothelin receptor subtype B (ET-RB), is known to be one of the many mediators that play a role in angiogenesis.1 For example, it has been shown that ET-1, acting via ET-RB and in concert with vascular endothelial growth factor (VEGF), promotes proliferation, migration and invasion of umbilical vein endothelial cells (HUVECs).2 The ET axis has also been found to be over-expressed by cancer cells and there is evidence that it is involved, in association with VEGF and other factors, in tumour angiogenesis.3 For example, in ovarian cancer, ET-1 stimulates early neovascularisation (proliferation and migration of endothelial cells) via ET-RB receptors.4 The ET system also plays a less direct role in angiogenesis by, for example, breaking down the extracellular matrix.3,5 Studies have linked increased tumour vascularity to ET-1 in brain tumours, ovarian and colorectal cancer,4,6,7 and in a ...
Introduction. Endothelin-1 (ET-1), together with its cognate receptors endothelin receptor subtype A (ET-RA) and endothelin receptor subtype B (ET-RB), is known to be one of the many mediators that play a role in angiogenesis.1 For example, it has been shown that ET-1, acting via ET-RB and in concert with vascular endothelial growth factor (VEGF), promotes proliferation, migration and invasion of umbilical vein endothelial cells (HUVECs).2 The ET axis has also been found to be over-expressed by cancer cells and there is evidence that it is involved, in association with VEGF and other factors, in tumour angiogenesis.3 For example, in ovarian cancer, ET-1 stimulates early neovascularisation (proliferation and migration of endothelial cells) via ET-RB receptors.4 The ET system also plays a less direct role in angiogenesis by, for example, breaking down the extracellular matrix.3,5 Studies have linked increased tumour vascularity to ET-1 in brain tumours, ovarian and colorectal cancer,4,6,7 and in a ...
Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. It is synthesized and released from endothelial cells and acts upon two receptor subtypes designated as ETA and ETB. In this study, a series of potent dipeptide sulfonamide dual-
TY - JOUR. T1 - Endothelin antagonism reduces circulating galectin-3 in patients with proteinuric chronic kidney disease. AU - Farrah, Tariq E. AU - Anand, Atul. AU - Miller-Hodges, Eve. AU - Mills, Nicholas L. AU - Webb, David J. AU - Dhaun, Neeraj. PY - 2018/1. Y1 - 2018/1. KW - Endothelin Receptor Antagonists. KW - Endothelins. KW - Galectin 3. KW - Humans. KW - Proteinuria. KW - Renal Insufficiency, Chronic. U2 - 10.1016/j.kint.2017.10.009. DO - 10.1016/j.kint.2017.10.009. M3 - Letter. C2 - 29291821. VL - 93. SP - 270. JO - Kidney International. JF - Kidney International. SN - 0085-2538. IS - 1. ER - ...
It is established that peptidemimetic drugs, such as renin inhibitors, somatostatin analogs, and endothelin antagonists, are often efficiently excreted into the bile in an unchanged form, resulting in their low bioavailability (Bertrams et al., 1991a,b;Greenfield et al., 1989; Nakamura et al., 1996). However, the present study shows that both the CLtotal andCLbile, p differ between various endothelin antagonist. Compound A has a 4-fold lowerCLtotal than that of BQ-485 (Table 1).CLbile, p also differs between each compound, with an 8-fold difference between compound A and BQ-485 (Table 1). The inhibition constant of compound A for binding to ETA is in the nanomolar range, as in the case of BQ-485 and BQ-123 (22, 3.4, and 13 nM for BQ-123, BQ-485, and compound A, respectively) (Fukami et al., 1996; Itoh et al., 1993; Moreland et al., 1994). This means that it is possible to construct a small peptide, like compound A, that exhibits relatively lower hepatic extraction but still has potent antagonist ...
Since its discovery in 1988, endothelin (ET) has been widely implicated in the pathophysiology of cardiovascular disease. ET antagonists have favourable effects in experimental models of these...
TY - JOUR. T1 - β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium. AU - Walker, C. A.. AU - Ergul, A.. AU - Grubbs, A.. AU - Zile, M. R.. AU - Zellner, J. L.. AU - Crumbley, A. J.. AU - Spinale, F. G.. PY - 2001. Y1 - 2001. N2 - Background: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in β-adrenergic receptor (β-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on β-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. Methods and Results: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10−6 to 0−9 mol/L) as well as after ...
The pathogenesis of hypertension is distinct between men and women. Endothelin-1 (ET-1) is a potential contributor to sex differences in the pathophysiology of hypertension. ET-1 participates in blood pressure regulation through activation of endothelin A (ETA) and endothelin B (ETB) receptors including those in the vasculature. Previous studies demonstrated that sex and sex hormones evoke discrepancies in ET-1-mediated control of vascular tone in different vascular beds. However, little is known about sex- and sex hormone-related differences in ET-1-dependent renal microvascular reactivity. Accordingly, we hypothesized that loss of sex hormones impairs afferent arteriole reactivity to ET-1. Male and female Sprague Dawley rats were subjected to gonadectomy or sham surgery (n = 6/group). After 3 weeks, kidneys from those rats were prepared for assessment of renal microvascular responses to ET-1 (ETA and ETB agonist, 10−12 to 10−8 M) and sarafotoxin 6c (S6c, ETB agonist, 10−12 to 10−8 M) using the
The IUPHAR/BPS Guide to Pharmacology. ETA receptor - Endothelin receptors. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Fingerprint Dive into the research topics of Affinity labelling of endothelin receptor and characterization of solubilized endothelin-endothelin‐receptor complex. Together they form a unique fingerprint. ...
We are interested in developing an airway explant culture system using sheep bronchi in which to establish respiratory viral infection and from which tissue can be used for functional, biochemical and immunohistochemical studies involving the endothelins (ETs). Freshly harvested sheep bronchial airway smooth muscle contains a homogeneous population of the ETA receptor. However, the potency of ET-1 and maximum contractile response of sheep bronchial explants to ET-1 increased with time in culture, despite these parameters remaining constant for carbachol in explants maintained for up to 48h. The possibility that this was caused by changes in ET receptor density was assessed using light microscopic quantitative autoradiography. In view of the increased responsiveness to ET-1 in cultured explants, it was surprising to demonstrate a significant decrease in total ET receptor (59±6% compared with the initial value, n = 4-5; P,0.01) and ETA receptor (51±2% compared with the initial value, n = 4-5, ...
AIM: Peripheral artery disease results in impaired blood flow to the extremities, most often as a consequence of atherosclerotic disease. The hallmark of atherosclerosis is chronic inflammation in the vessel wall. The renin-angiotensin and endothelin systems are considered important pathophysiological effectors. Midkine, a multifunctional cytokine, fulfils different roles in inflammation and promotion of neoangiogenesis. The aim of this study was to assess whether circulating midkine serum levels in patients with peripheral artery disease correlate with established atherosclerosis risk factors, as well as titers of functional autoantibodies directed against receptors of the renin-angiotensin and endothelin system ...
The contribution of the endothelin system to BP regulation in the SHR is controversial, but the present work appears to be the first in which BP was measured by radiotelemetry. We found that bosentan per se failed to induce any change in BP in both rat strains. The bosentan was active because it antagonized the effects of exogenous administration of ET-1 in conscious rats (Fig 2⇑) and the tension responses to ET-1 in ring preparations of rat aorta (Table 2⇑) in a competitive fashion. These results parallel those of other researchers.6 7 In contrast to our findings with bosentan, both BQ-123, an ETA antagonist, and SB 209670, a nonselective ETA/ETB antagonist, have been reported to reduce BP in SHR8 9 and transgenic rats10 when infused over prolonged periods. On the other hand, other researchers have reported no change of BP with BQ-123 and bosentan in SHR.11 12 Pressure in these previous studies was monitored with exteriorized catheters or by the tail-cuff method. Control BP values are ...
Principal Investigator:NINOMIYA Haruaki, Project Period (FY):1998 - 2001, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:General pharmacology
units with a pulmonary capillary wedge pressure < 15 mmHg 8,10. TREATMENT SSc-associated PAH previously had a poor prognosis with a one-year survival rate of 45%. Poor survival has significantly increased with modern treatments such as prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Drugs used in PAH 1) Prostanoids a)Epoprostenol: Starting dose of infusion is 1-2 ng/kg per minute, gradually increased up to 25-40 ng/kg per minute b) Treprostinil: given as a continuous subcutaneous or intravenous infusion in patients with PAH from functional class II, III and IV Dose:1.25 ng/kg per minute 2).Endothelin receptor antagonists a)Bosentan: It is indicated for PAH functional classes II, III and IV. Dose: 62.5 mg bid for 4 weeks before titration up to 125-250 mg bid b) Ambrisentan: Dose: 2.5-10 mg Ambrisentan in combination with tadalafil reduces the risks of disease progression and hospitalization for worsening PAH and improves exercise ability. 3)PDE inhibitors a) ...
Name: Beta-blockers and ace inhibitors as combination therapy for heart failure or endothelin receptor antagonist and ace inhibitors as combination therapy for heart failure Course: Lecturer: Date Table of Content ABSTRACT 2 INTRODUCTION 3 Background to the Study 3 Purpose of the Study 4 Research Questions 4 Significance of the Study 4 LITERATURE REVIEW 5 Literature Search Approach 5 Current trend in cases of heart failure 6 Systolic Dysfunction in Heart Failure: Neurohormonal Theory 7 Beta blocks and their functions 8 ACE inhibitors and their functions 9 Endothelin receptor antagonists and their functions 10 RESULTS 11 Selection of Patients for Beta-Blockers and ACE Inhibitor combination 12 ...
Results Ninety-eight patients (initial ERA=24, initial PDE5=59, initial ERA/PDE5=15) were included; no significant differences in baseline variables existed. TTCW was significantly worse in patients initially started on ERA compared to PDE5 or ERA/PDE5 (p=0.0001). Baseline factors independently associated with shorter TTCW were initial ERA (HR 2.63, p=0.009), lower DLCO (HR 0.69 per 10% change, p=0.04), and higher PVR (HR 1.10 per Wood unit change, p=0.007). Three year survival was significantly worse in the initial ERA group (52.9%) compared to the PDE5 (91.5%) or ERA/PDE5 group (92.9%, p=0.004). The only baseline factor independently associated with risk for death in this cohort was initial ERA therapy (HR 4.55, p=0.004). ...
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
The current understanding of the mechanisms of action of insulin and cellular interactions of insulin with endothelin supports an expectation for both vascular and nonvascular effects of endothelin antagonism on insulin action. The discovery of endothelin as a vasoconstrictor agent produced by the endothelium prompted initial explorations of its role as a modulator of vascular function (39). The net tissue actions of insulin in skeletal muscle depend in part on the capacity of the vasculature to vasodilate in response to insulin (12,40,41), with this vasodilation actively redistributing blood flow in support of the increased metabolism (13). This vascular action of insulin is impaired in states of insulin resistance (9,42,43), and we and others have previously shown that increased endogenous endothelin contributes to vascular dysfunction in obesity and diabetes (7,8). Based on these observations, we had an a priori expectation that endothelin antagonism would improve insulin-stimulated ...
Endothelin A Receptor: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.
Biological Description: Macitentan(ACT064992) is an orally active, non-peptide dual endothelin ETA and ETB receptor antagonist for the potential treatment of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).IC50 value: Target: ETA/ETB ...
Ambrisentan belongs to the group of medications called endothelin receptor antagonists. These medications block the action of endothelin in the arteries of the lung that causes blood vessels to tighten or constrict. Ambrisentan is used to treat the symptoms of primary pulmonary arterial hypertension (PAH), or high blood pressure in the arteries of the lungs.
Supplementary MaterialsSupplementary Information 41467_2020_16637_MOESM1_ESM. Small RNA profiling reveals that miR2118-dependent 21-nucleotide (nt) phasiRNAs in the anther wall are?U-rich, distinct from the phasiRNAs in germ cells. Furthermore, the miR2118-dependent biogenesis of 21-nt phasiRNAs may involve the Argonaute proteins OsAGO1b/OsAGO1d, which are abundant in anther wall NRAS cell layers. Our study highlights the site-specific differences of phasiRNAs […]. ...
Principal Investigator:SHIGEMATSU Kazuto, Project Period (FY):1997 - 1998, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Experimental pathology
Learn more about OPSUMIT® (macitentan), an endothelin receptor antagonist, including PAH (WHO Group 1) disease education, and more.
GPR37 antibody (G protein-coupled receptor 37 (endothelin receptor type B-like)) for IHC-P. Anti-GPR37 pAb (GTX85872) is tested in Human samples. 100% Ab-Assurance.
Dear Abby: My wife sleeps in the raw. Then she showers, brushes her teeth and fixes our breakfast -- still in the buff. Were newlyweds and there are just the two of us, so I suppose theres really nothing wrong with it. What do you think? -- Ed. Dear Ed: Its OK with me. But tell her to put on an apron when shes frying bacon.. Dear Abby: My boyfriend is going to be 20 years old next month. Id like to give him something nice for his birthday. What do you think hed like? -- Carol. Dear Carol: Nevermind what hed like, give him a tie.. Dear Abby: What inspires you most to write? -- Ted. Dear Ted: The Bureau of Internal Revenue.. Dear Abby: Ive been going with this girl for a year. How can I get her to say yes? -- Don. Dear Don: Whats the question?. Dear Abby: Our son married a girl when he was in the service. They were married in February and she had an 8 1/2-pound baby girl in August. She said the baby was premature. Can an 8 1/2-pound baby be this premature? -- Wanting to Know. Dear ...
Dear Sir in column A i have the following Column A Column B (ResultColumn C ) 1 5 5 -2 7 -7 3 -9 9 -4 -10 -10 5 -2 - Microsoft Office Excel 2003 for PC question
Emily Yoffe, aka Dear Prudence, is on Washingtonpost.com weekly to chat live with readers. (Sign up here to get Dear Prudence delivered to your inbox...
I had a few other issues to discuss with him but overall the neurologist felt that Dear Son had deteriorated significantly and that his disease is progressing. In light of that, he asked me what I wanted to do regarding the surgery and I said that I didnt want to drive that issue. We talked some more and I asked him if we were to do the surgery, is this something we need to do now or later and he felt if we did it, we should do it now since he wont be able to manage it later. He told me that there is a chance Dear Son would need to be intubated after the surgery and that the intubation could be quite lengthly. He explained that Dear Son will die of respiratory issues. I did not get the sense that he felt Dear Son would really make it through the surgery even though the ENT thought the surgery was doable. I also had some difficulty in doing a surgery so soon after we had been released. My gut tells me that Dear Son would not survive this surgery. I saw how hard it was in November for him to ...
DEAR ABBY: I have acquired two teenage stepsons. They are good young men, mature, responsible, active in community service and good in school and sports.
DEAR ABBY: When my 9-month-old grandson, Eli, comes to visit, I become frustrated to the point of leaving the room, if not my house. Not only must we put away things he shouldn t get into, we must tape shut every drawer and cabinet, block access behind
The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10-10 M to 10-6 M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3×10-7 M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10-10 M to 10-6 M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10-7 M to 10-5 M) produced a marked shift to the right of the ET-1 concentration-response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2 = 7.96; slope = 0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10-7 M to 10-5 M) had no effect ...
article{b53dd734-d576-42ed-8e0f-a70425b980ab, abstract = {The aim of this study was to examine if endothelin ETB receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ETB receptors was studied by measuring the change in isometric tension in rings of left anterior descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ETB receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbeccos Modified Eagles Medium, Sarafotoxin 6c induced a concentration dependent contraction with pEC(50) value of 10.4 +/- 0.21 and a maximal response of 3.9 +/- 0.25 mN/mm (n = 15). The maximal contraction was significantly larger than the responses measured in fresh tissue, where the mean value of the maximal contractions was 0.22 +/- 0.03 mN/mm (n = 17). The increased contraction to Sarafotoxin 6c, after culturing could be eliminated ...
About one third of patients with type 1 diabetes develops kidney disease. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. Endothelin type B receptors (ETB-R) can induce vasodilation of the renal vasculature and also regulate tubular sodium handling. However, the role of ETB-R in kidney oxygen homeostasis is unknown. The effects of acute intrarenal ETB-R activation (Sarafotoxin 6c for 30-40 min; 0.78 pmol h-1 directly into the renal artery) on kidney function and oxygen metabolism were investigated in normoglycemic controls and insulinopenic male Sprague Dawley rats ...
About one third of patients with type 1 diabetes develops kidney disease. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. Endothelin type B receptors (ETB-R) can induce vasodilation of the renal vasculature and also regulate tubular sodium handling. However, the role of ETB-R in kidney oxygen homeostasis is unknown. The effects of acute intrarenal ETB-R activation (Sarafotoxin 6c for 30-40 min; 0.78 pmol h-1 directly into the renal artery) on kidney function and oxygen metabolism were investigated in normoglycemic controls and insulinopenic male Sprague Dawley rats ...
TY - JOUR. T1 - Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate. AU - Inman, Sharon R.. AU - Burns, Thomas E.. AU - Plott, Wanda K.. AU - Pomilee, Ray A.. AU - Antonelli, Jodi A.. AU - Lewis, Richard M.. PY - 2002/7/27. Y1 - 2002/7/27. N2 - Background. Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after ...
TY - JOUR. T1 - Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure. AU - Fratz, Sohrab. AU - Meyrick, Barbara. AU - Ovadia, Boaz. AU - Johengen, Michael J.. AU - Reinhartz, Olaf. AU - Azakie, Anthony. AU - Ross, Greg. AU - Fitzgerald, Robert. AU - Oishi, Peter. AU - Hess, John. AU - Black, Stephen M.. AU - Fineman, Jeffrey R.. PY - 2004/9/1. Y1 - 2004/9/1. N2 - Endothelin receptor blockade is an emerging therapy for pulmonary hypertension. However, hemodynamic and structural effects and potential changes in endogenous nitric oxide (NO)-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in pulmonary hypertension secondary to congenital heart disease are unknown. Therefore, the objectives of this study were to determine hemodynamic and structural effects and potential changes in endogenous NO-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in a lamb model of increased pulmonary blood flow following in ...
TY - JOUR. T1 - Renal vasoconstriction to endothelin-1 is enhanced with blockade of endothelin-B receptors or nitric oxide production. AU - Stacy, D. L.. AU - Martinez, R.. AU - Tilton, Ronald. PY - 1996. Y1 - 1996. N2 - Endothelin (ET-1) is a potent renal vasoconstrictor causing an initial transient vasodilation due to activation of ETB receptors and a long-lasting vasoconstriction thought to be due to ETA and ETB receptors. In anesthetized rats ET-1 was infused intravenously {i.V., 1 nmole/kg) after BQ-123 (an ETA receptor antagonist), BQ-788 (an ETB receptor antagonist), or vehicle. Left renal artery flow and mean arterial pressure (MAP) were measured. Resistance was calculated as MAP/flow. ET-1 increased renal resistance by 248% (26±2 to 90±13 mmHg/ml/min.). After pretreatment with BQ-123 (1 mg/kg, i.V.), the increase in renal resistance with ET-1 was reduced by 77% (29±5 to 43±7 mmHg/ml/min.), due to a reduction in the increase in MAP by 81% and decrease in flow by 61%. Pretreatment ...
295329207 - EP 1009741 A1 2000-06-21 - NOVEL CARBOXYLIC ACID DERIVATIVES, THEIR PRODUCTION AND THEIR USE AS MIXED ET A?/ET B? ENDOTHELIN-RECEPTOR ANTAGONISTS - [origin: WO9911629A1] The invention relates to carboxylic acid derivatives of formula (I) wherein the radicals are defined in the description, and to the use of these derivatives as ETA/ETB endothelin-receptor antagonists.[origin: WO9911629A1] The invention relates to carboxylic acid derivatives of formula (I) wherein the radicals are defined in the description, and to the use of these derivatives as ETA/ETB endothelin-receptor antagonists.
A highly selective peptide agonist of the endothelin-B receptor. Endothelin B receptor agonist SPI-1620 binds to endothelin-B receptors on endothelial cells in tumor blood vessels, which, unlike the angioarchitecture of normal blood vessels, are relatively devoid of smooth muscle. This agent may induce a transient, selective increase in blood flow to a tumor, which may result in an increase in the delivery of anticancer agents to the tumor and, so, an increase in anticancer agent efficacy.. ...
United States Endothelin Receptor Antagonist Market Report 2016 is a market research report available at US $3800 for a Single User PDF License from RnR Market Research Reports Library.
In the present study, chronic administration of bosentan, an antagonist of both ETA and ETB receptors, had no significant effect on the systolic BP level reached after 6 weeks of L-NAME treatment, confirming the observation that acute (60 minutes) administration of the selective ETA receptor antagonist BQ-123 could not lower BP in rats treated for 3 weeks with an l-arginine analogue.21 However, the delay in the BP elevation occurring when bosentan was added to L-NAME would suggest that ET is involved in the early hypertensive response to the l-arginine analogue. This observation is in line with studies showing a blunted hypertensive effect of acute L-NAME administrations by ET receptor antagonists12 13 14 and provides experimental evidence to explain the discrepancy in the efficacy of ET receptor antagonists in acute and chronic L-NAME-induced hypertension.. Chronic administration of L-NAME leads to eutrophic remodeling of the basilar artery, as we previously reported.15 The structural ...
There are no specific protocols for Recombinant Human Endothelin B Receptor protein (ab114259). Please download our general protocols booklet
In the RITZ-4 trial, the effect of tezosentan in patients with acute decompensated heart failure associated with acute coronary syndromes was evaluated.43 In this multicenter, randomized, double-blind trial, 193 patients were randomized to receive intravenous 25 mg tezosentan per hour for the first hour and then 50 mg per hour up to 48 hours or placebo. The primary end point was a composite of death, worsening heart failure, recurrent ischemia, and recurrent or new myocardial infarction within 72 hours. No significant differences were observed between the group receiving tezosentan and placebo in the composite primary end point. Symptomatic hypotension was more frequent in the treatment group.. The RITZ-5 trial evaluated the addition of intravenous tezosentan to standard therapy for patients presenting with acute pulmonary edema.44 In this trial, all patients received oxygen through a face mask, intravenous morphine, furosemide, and a continuous drip of isosorbide dinitrate according to their ...
The vascular effects of the endothelin B (ETB) receptor agonist IRL 1620 were investigated in the rat P22 carcinosarcoma and a range of normal tissues in BDIX rats. Tissue blood flow rate was calculated from measurements of tissue uptake of radiolabelled iodoantipyrine. A comparison of vascular effects in the P22 tumour and the HSN sarcoma growing in CBH/CBi rats was made using laser Doppler flowmetry, showing similar effects of IRL 1620, with red cell flux rapidly decreasing by 50-60% and then returning to control levels within approximately 30 min. This corresponded to similar levels but different spatial organisation of ETB binding sites in the two tumours, as measured by autoradiography. The decrease in tumour blood flow and an increase in vascular resistance suggest that the vascular component of ETB receptors in the P22 tumour is localised on contractile elements rather than on endothelial cells. ETA receptors were also identified. Vasoconstriction occurred uniformly throughout the P22 ...
BioAssay record AID 66868 submitted by ChEMBL: Inhibition of (125 I)-endothelin 1 binding to endothelin B receptor in rat cerebellum.
Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.
METHODS AND RESULTS Experiments were performed on rats at 1 through 16 weeks after sham operation or coronary artery ligation. Rats with left ventricular end-diastolic pressures , 15 mm Hg were considered to have chronic heart failure (CHF), while the others were considered to have uncomplicated myocardial infarction (MI). There were increased ET-1 concentrations in CHF rats at weeks 1 to 16 (Sham, 20 +/- 0.5 pg/mL, n = 45; CHF, 31 +/- 2 pg/mL, n = 50; P , .001) and transient increases in ET-3 concentrations at week 1 in both the MI and CHF groups. There were no significant increases in big ET-1 concentrations, suggesting an increased conversion of ET-1 from big ET-1 in the CHF group. At weeks 2 through 8, oral administration of the mixed (ETA and ETB) endothelin receptor antagonist bosentan significantly decreased mean arterial pressure in conscious CHF rats, an effect that increased over time. Furthermore, bosentan had an additive effect to the angiotensin-converting enzyme inhibitor ...
EDNRB - EDNRB (Myc-DDK-tagged)-Human endothelin receptor type B (EDNRB), transcript variant 3 available for purchase from OriGene - Your Gene Company.
Recent gene targeting studies have revealed unexpected roles for endothelins in the development of neural crest-derived tissues. Endothelin converting enzyme-1 (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to endothelin-1(ET-1) in vitro. However, the importance of ECE-1 cleavage in the multiple endothelin pathways in vivo is unknown. Here we generated a targeted null mutation in the mouse ECE-1 gene. ECE-1−/− term embryos exhibited craniofacial and cardiac abnormalities virtually identical to the defects seen in ET-1 and endothelin A receptor (ETA)-deficient embryos. Epidermal melanocytes as well as enteric neurons of the distal gut were also absent in ECE-1−/− embryos, reproducing the developmental phenotype seen in ET-3−/− and endothelin B receptor (ETB)−/− mice. Surprisingly, large amounts of mature ET-1 peptide are found in ECE-1−/− embryos, indicating that non-ECE-1 protease(s) can activate ET-1 at certain sites. However, these enzymes cannot produce ...
Microvascular dysfunction originating during a preeclamptic pregnancy persists postpartum and probably contributes to increased CVD risk in these women. One putative mechanism contributing to this dysfunction is increased vasoconstrictor sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type-B (ETBR). We evaluated ET-1 sensitivity, ETAR, and ETBR contributions to ET-1-mediated constriction, and the mechanistic role of ETBR in endothelium-dependent dilation in vivo in the microvasculature of postpartum women who had preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=12). We hypothesized that (1) PrEC would have a greater vasoconstrictor response to ET-1, and (2) reduced ETBR-mediated dilation. We further hypothesized that ETBR-blockade would attenuate endothelium-dependent vasodilation in HC, but not PrEC. Microvascular reactivity was assessed by measurement of cutaneous vascular conductance responses to graded infusion of ET-1 ...
LifeSpan BioSciences currently sells 33 antibodies , 5 peptides , 11 ELISA Kits , 4 proteins specific for EDNRB / Endothelin B Receptor.
Buy our Endothelin B Receptor peptide. Ab109654 is a blocking peptide for ab95911 and has been validated in BL. Abcam provides free protocols, tips and expert…
Endothelin B Receptor Polyclonal Antibody from Invitrogen for Western Blot and Immunohistochemistry (Paraffin) applications. This antibody reacts with Human, Mouse, Rat samples. Supplied as 100 µL purified antibody (1 mg/ml) in PBS with 50% glycerol and 0.01% thimerosal; pH 7.
When Yanagisawa et al.1 first identified endothelin (ET), a novel polypeptide vasoconstrictor for which numerous other functions were identified later,2 there was early widespread enthusiasm and great expectation for therapeutic opportunities. ET-1 is the most powerful vasoconstrictor in this peptide family; the ET system is complex with a converting enzyme and two receptors, ETA-R and ETB-R. The receptors offer an opportunity for selective blockade. ETA-R primarily mediates vasoconstriction and plays a role in the genesis of hypertension, states of endothelial dysfunction, insulin resistance, inflammation, and fibrosis. From a renal perspective, it is important to note that both ETA-R and ETB-R are found in the kidney, ETA-R in vessels and ETB-R mainly in the medulla3 but also in glomeruli.4 Of note, collecting duct ETB-R null mice develop elevated BP, pointing to a potential causal role in the genesis of hypertension.5 It was immediately perceived that such a multifunctional system might ...
Since its discovery in 1988 the powerful vasoconstrictor endothelin-1 (ET-1) has been widely implicated in the pathophysiology of chronic kidney disease (CKD) as well as the cardiovascular disease with which it is associated. ET receptor antagonists have favourable effects in experimental models of these conditions and orally acting antagonists are now licensed for the treatment of pulmonary arterial hypertension. However, there is a paucity of human data regarding the role of ET-1 in CKD. In this thesis, I have therefore explored the utility of ET-1 as a biomarker in CKD, and, using selective ET receptor antagonists, the beneficial renal and cardiovascular effects of ET receptor antagonism in CKD. I have shown that as glomerular filtration rate (GFR) declines plasma ET-1 increases linearly whereas urinary ET-1 shows an exponential increase. Furthermore, urinary ET-1 may be a useful marker of disease activity in patients with lupus nephritis. Its levels are high in those with biopsy-proven ...
TY - JOUR. T1 - Elevated urinary excretion of endothelin in insulin-dependent diabetes mellitus. T2 - No influence of physical exercise. AU - Mattyus, I.. AU - Zimmerhackl, L. B.. AU - Schwarz, A.. AU - Brandis, M.. AU - Miltényi, M.. AU - Tulassay, T.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - The urinary excretion of endothelin was measured by radioimmunoassay in children with diabetes mellitus in metabolically stable condition before and after ergometric exercise. Apparently healthy children served as normal controls. The excretion of endothelin, calculated for 24h and the ratio of endothelin/creatinine in urine were also significantly higher in diabetic children compared to normal controls. Physical exercise had no influence on renal endothelin excretion. In-diabetic children the volume of diuresis was higher compared to controls. Physical exercise had no influence on diuresis. In a previous study we found a positive correlation between diureses and endothelin excretion. Therefore, the increased ...
Endothelins are potent endothelium-derived vasoconstrictors 1. The endothelin system has been reported to be activated in various types of experimental or clinical pulmonary hypertension 1. However, whether endogenous endothelins play a role in the control of systemic and pulmonary vascular tone in vivo remains uncertain. Endothelin receptor antagonists have been shown to increase forearm blood flow in humans 2, 3, to reduce brachial artery pressure in patients with essential hypertension 4 and to decrease pulmonary artery pressure in patients with primary pulmonary hypertension 5, 6. However, some investigators have been unable to demonstrate pulmonary or systemic vascular effects of these compounds in vivo 7-17. The failure to show a vasoconstrictor effect of endogenous endothelins appears related, at least in part, to the release of nitric oxide (NO) by the endothelium, which either counteracts the effect and/or inhibits the synthesis of endothelins 16-19.. Endothelins have been hypothesised ...
The current in vitro studies demonstrate an enhanced vasoconstrictor response of small coronary arteries to ET-1 and S6c in pigs with experimental hypercholesterolemia. This response is mediated mainly through the ETB receptor. These alterations in the coronary responsiveness occurred in the setting of long-term elevation of circulating ET-1. These studies support a role for both the ETA and ETB receptors in the regulation of coronary tone in the presence and absence of hypercholesterolemia.. Seo and colleagues12 previously demonstrated that the contractile response of porcine epicardial arteries to endothelins is biphasic; the first phase attained at low concentrations is primarily mediated by the endothelin ETB receptor, whereas both endothelin receptors mediate contraction in the latter, more pronounced phase attained at high concentrations. Takase and colleagues32 found similar results in noncoronary resistance vessels. The current studies extend these previous observations and demonstrate ...
This article is within the scope of WikiProject Pharmacology, a collaborative effort to improve the coverage of Pharmacology on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks ...
Object. The disturbed balance between nitric oxide and endothelin (ET)-1 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ETA receptor-dependent contractile effect, ET-1 also has ETB receptor-mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ETA receptor-selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature.. Methods. Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10−9 to 10−6 M) after a precontraction was induced by prostaglandin F2α. The inhibition by clazosentan was ...
The present invention relates to new pyridine sulfonamide modulators of endothelin-A receptor, pharmaceutical compositions thereof, and methods of use thereof. |p||chemistry id=CHEM-US-00001 num=00
Endothelins are potent peptide vasoconstrictors which were discovered two decades back. Their role in cardiovascular diseases, cancer, glaucoma, diabetes mellitus and many other diseases have been studied. Inspite of a lot of research many questions regarding their pathophysiological roles still remain unanswered. Though many endothelin receptor antagonists showed promising results in animal studies they failed to show significant improvement in clinical practice. The limitations of receptor antagonists lead to the research on synthesis inhibitors and their combinations with ACE inhibitors. This article summarizes the path of endothelins from their discovery to their current status and future prospects.. ...
There is a clear association between air pollution exposure and cardiovascular mortality. However, the mechanisms linking air pollution to cardiovascular events are poorly understood. Inhalation of particulate matter (PM) air pollution has been shown to increase the release of vasoactive cytokines such as endothelin while individuals with vascular disease have augmented vasoconstrictor responses to this peptide. Therefore, diesel exhaust-released endothelin could contribute to air pollution-induced cardiovascular events in sensitized individuals. We propose to use a novel model of endothelin dependent hypertension and endothelial dysfunction, paired with state-of-the-art methods for generating whole diesel exhaust, to investigate cardiovascular effects of PM. Our recent studies demonstrate that simulating sleep apnea by exposing rats to 90 second episodes of intermittent hypoxia/hypercapnia (IH) for 8 hours a day causes hypertension that is reversed by endothelin antagonists and associated with ...
TY - JOUR. T1 - Endothelin mediated contraction of equine laminar veins. AU - Keen, John A.. AU - McGorum, Bruce C.. AU - Hillier, Chris. AU - Nally, Jane E.. N1 - Originally published in: Equine Veterinary Journal (2008), 40 (5), pp.488-492.. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Endothelin-1 (ET-1) may be a key mediator in the pathogenesis of laminitis, but endothelin-mediated responses in the venous microcirculation of the equine foot have yet to be fully characterised. The aim of this study was to characterise the response of equine laminar veins to ET-1 and evaluate the ET-1 receptor subtypes that mediate this response. Small veins (150-500 µm) draining the equine digital laminae from healthy horses and ponies subjected to euthanasia at an abattoir were investigated using wire myography. Concentration response curves were constructed for ET-1 in the presence of ETA (BQ123) and ETB (BQ788) receptor antagonists, and L-NAME, a nitric oxide synthase blocker. The selective ETB receptor agonist ...
mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulins enhanced antiatherogenic actions in EC was related to remarkable induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca2+]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1 overexpression in the endothelia of ...
Ednrb - Ednrb (untagged ORF) - Rat endothelin receptor type B (Ednrb), (10 ug) available for purchase from OriGene - Your Gene Company.
Various tissues including heart express specific binding sites for endothelin. Endothelins have been reported to increase the force of contraction of cardiac muscle, presumably via specific receptors. Specific binding of endothelin to atrial tissue is particularly high. In spontaneously contracting rat atrial cells used in this study, all three isoforms of endothelin (endothelin-1, endothelin-2, and endothelin-3) decreased the rate of beating and caused an increase in inwardly rectifying K+ current in voltage-clamped whole cells. Endothelin-3 was the most potent isoform, and its effects on beating rate and K+ current were present at a concentration as low as 100 pM (Kd, approximately 1 nM). the atrial cells did not have the hyperpolarization-activated current (the pacemaker current), If. In excised inside-out patches, all three isoforms of endothelin activated a population of K+ channels with kinetic properties identical to those of acetylcholine (muscarinic)-activated K+ channels, and this was ...
Injury to the eye or retina triggers Muller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Muller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Muller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Muller cells as well as the human Muller cell line MIO-M1. The Muller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in ...
Endothelins (ET-1, 2, and 3) are considered to be very powerful vasoconstrictive substances. In humans, endothelins mediate their actions via two…
Activation of the endothelin A receptor (ET(A)) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ET(A) may have anticancer effects, while retaining beneficial endothelin B receptor (ET(B))-mediated effects such …
We previously reported that the in vitro inhibitory effects of several OATP1B1 inhibitors showed remarkable substrate-dependence using prototypical substrates, E2G, E1S, and BSP (Izumi et al., 2013). In addition to the prototypical substrates, clinically used OATP1B1 substrate drugs could also serve as in vitro OATP1B1 probe substrates, for which the potential substrate-dependent inhibition has not been comprehensively evaluated. To identify representative in vitro OATP1B1 probe substrates that could mitigate the risk of false-negative DDI prediction, this study investigated the impact of in vitro substrate selection on OATP1B1 inhibition and the subsequent DDI prediction for 12 clinically used OATP1B1 substrate drugs compared with the prototypical probe substrates.. Twelve OATP1B1 substrate drugs-including statins (pitavastatin, atorvastatin, fluvastatin, rosuvastatin, and pravastatin), antidiabetics (repaglinide, nateglinide, and glibenclamide), a dual endothelin receptor antagonist ...
Endothelin is the most potent constrictor of human blood vessels known to man. In mammals, there are three structurally and pharmacologically separate ET isopeptides: ET-1, ET-2, and ET-3 (Volpe 46). Endothelin-1 is the primary isoform in the human cardiovascular system and is a 21-amino acid peptide produced chiefly by endothelial cells (Lüscher 2434). Endothelin-converting enzymes (ECE), chymases, and non-ECE metalloproteases are responsible for the synthesis of ET-1 by means of autocrine regulation (Lüscher 2434). ET-1 operates through the initiation of two G-protein coupled receptors: ETA and ETB. Located on vascular smooth muscle cells, ETA receptors regulate vasoconstriction and cell proliferation. ETB receptors, situated on endothelial cells, mediate endothelium-dependent vasodilation through the release of nitric oxide and prostacyclin (Haapaniemi 721). In addition to its cardiovascular and mitogenic effects, endothelin-1 is involved in gastrointestinal and endocrine function, ...
Endothelin receptor antagonists[edit]. Moderate quality evidence suggests that endothelin receptor antagonists improve exercise ... Endothelin[edit]. Endothelin-1 is a peptide (comprising 21 amino acids) that is produced in endothelial cells. It acts on the ... Three of these pathways are important since they have been targeted with drugs - endothelin receptor antagonists, ... "Endothelin receptor antagonists for pulmonary arterial hypertension". Cochrane Database of Systematic Reviews. doi:10.1002/ ...
endothelin. ↑endothelin receptor ETA angiotensin II. ↑Angiotensin receptor 1 *On smooth muscle cells: Activation of Gq --, ↑PLC ... Various receptors on endothelium[6]. Endothelin production[6] Pathology[edit]. Vasoconstriction can be a contributing factor to ... P2X receptor. ↑Ca2+ NPY. NPY receptor Activation of Gi --, ↓cAMP --, ↓PKA activity --, ↓phosphorylation of MLCK --, ↑MLCK ... α1 adrenergic receptor Activation of Gq --, ↑PLC activity --, ↑IP3 and DAG --, activation of IP3 receptor in SR --, ↑ ...
It is an endothelin receptor antagonist. Zibotentan was granted fast track status for the treatment of prostate cancer by the ... September 2011). "Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel ...
Characterization of receptors". Hypertension. 19 (2): 49-55. doi:10.1161/01.hyp.19.2_suppl.ii49. PMID 1735595. Phillips, PA. " ... "Interaction between endothelin and angiotensin II." Clinical and Experimental Pharmacology and Physiology. 26.7. (1999): 517- ... Indirectly, angiotensin II stimulates of the production of endothelin 1 and 3 (ET1, ET3) and the transforming growth factor ... Effects of angiotensin converting enzyme inhibition and angiotensin II type 1 receptor blockade". Basic Research in Cardiology ...
"Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist". J. Org. Chem. 64 (26): 9658. doi:10.1021/jo991292t. ...
Endothelin Okada, M; Nishikibe, M (Winter 2002). "BQ-788, a selective endothelin ET(B) receptor antagonist". Cardiovascular ...
The endothelin receptor B produces Waardenburg syndrome type IV. Discovering that the same gene is involved in both ABCD and ... It has been found to be caused by mutation in the endothelin B receptor gene (EDNRB). In the beginning, medical officials ... April 2008). "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in ... New findings introduced an important break in the beliefs about ABCD syndrome because the endothelin B gene is a gene involved ...
4-Diarylpyrrolidine-3-carboxylic AcidsPotent ETASelective Endothelin Receptor Antagonists. 1. Discovery of A-127722". Journal ...
... is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ETA). Ambrisentan significantly ... As such, endothelin receptor antagonists such as Ambrisentan are known to be teratogenic. Ambrisentan has a high risk of liver ... Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These ... In addition to this, endothelin receptors are also known to play a role in neural crest cell migration, growth, and ...
... (LU-135252; HMR-4005) is an endothelin receptor antagonist. Gilead Colorado, a subsidiary of Gilead Sciences, under ...
... is a selective ETA endothelin receptor antagonist. As such, it is used as a biochemical tool in the study of endothelin ... Atkinson RA, Pelton JT (January 1992). "Conformational study of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], an endothelin-A receptor- ... Büyükgebiz O, Aktan AO, Haklar G, Yalçin AS, Yeğen C, Yalin R, Ercan ZS (1996). "BQ-123, a specific endothelin (ETA) receptor ... Clavell AL, Stingo AJ, Margulies KB, Brandt RR, Burnett JC (March 1995). "Role of endothelin receptor subtypes in the in vivo ...
It is an endothelin receptor antagonist selective for subtype A (ETA). While other drugs of this type (sitaxentan, ambrisentan ... March 2008). "Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and ... May 2014). "The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy". ... atrasentan blocks endothelin induced cell proliferation.[citation needed] In April 2014, de Zeeuw et al. showed that 0.75 mg ...
1997). "Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor ... G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an ... 1998). "β2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor ... 2001). "Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function". J. Biol. ...
It is a dual endothelin receptor antagonist, see also: Endothelin receptor antagonist. Zavesca (miglustat): is currently the ... Uptravi is an oral medication that should be used along with a phosphodiesterase-5 inhibitor, an ERA(endothelin receptor ... Endothelin Receptor Antagonist) that has been used to slow down the prohibit the advancement of diseases and PAH. Actelion ... Actelion scientists were among the first to work in the field of endothelian receptor antagonists. Actelion was initially ...
Endothelin receptor antagonist, another class of drugs used in PAH "Background Riociguat". Bayer HealthCare. Archived from the ...
Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D (June 1998). "A dinucleotide mutation in the endothelin-B receptor ... Metallinos DL, Bowling AT, Rine J (June 1998). "A missense mutation in the endothelin-B receptor gene is associated with Lethal ... A mutation in the middle of the endothelin receptor type B (EDNRB) gene causes lethal white syndrome when homozygous. Carriers ... Such regulatory genes include endothelin receptor type B (EDNRB). A mutation in the middle of the EDNRB gene, Ile118Lys, causes ...
... epidermal growth factor receptor, endothelin receptor type B, PDGFRB, PDGFRA, PTGS2, TRAF2, estrogen receptor alpha, caveolin 2 ... Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (April 2003). "Regulated interaction of endothelin B receptor with caveolin-1". ... TGF beta receptor 1,endothelial NOS,androgen receptor,amyloid precursor protein,gap junction protein, alpha 1,nitric oxide ... Yamamoto M, Toya Y, Jensen RA, Ishikawa Y (March 1999). "Caveolin is an inhibitor of platelet-derived growth factor receptor ...
Ihara, M; Fukuroda, T; Saeki, T; Nishikibe, M; Kojiri, K; Suda, H; Yano, M (15 July 1991). "An endothelin receptor (ETA) ... Streptomyces misakiensis produces tubermycin A, tubermycin B, misakimycin and the endothelin receptor antagonist BE-18257B. ... "An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis". Biochemical and Biophysical Research ... "An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis". Biochemical and Biophysical Research ...
Small-molecule endothelin receptor antagonists: a review of patenting activity across therapeutic areas. IDrugs 12(6): 366-75 ( ... Sitaxentan for the Oral Treatment of Pulmonary Arterial Hypertension: Benefits from Endothelin Receptor Subtype Selectivity? ... and endothelin receptor antagonists. By 2009 Hermann Mucke had authored or co-authored about 50 peer reviewed original research ...
It has potent activity as an endothelin receptor antagonist and anti-osteoporosis agent. It also has strong cytotoxicity ...
"Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors". European ... Offermanns S, Schultz G, Rosenthal W (Feb 1991). "Evidence for opioid receptor-mediated activation of the G-proteins, Go and ... GNAI2 has been shown to interact with: EYA2, GPSM2, Interleukin 8 receptor, alpha, MDFI, RGS5, and RIC8A. GRCh38: Ensembl ... McClue SJ, Milligan G (Sep 1990). "The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108-15 ...
"Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal ... Endothelin-1 has two receptors in the pulmonary arterial tree, ET-A which mediates vasoconstriction and ET-B which mediates ... Kuntzen, C; Gülberg, V; Gerbes, AL (January 2005). "Use of a mixed endothelin receptor antagonist in portopulmonary ... Bosentan is a nonspecific endothelin-receptor antagonist capable of neutralizing the most identifiable cirrhosis associated ...
... and thus activate endothelin-receptors, endothelin receptor type A (ETA) and endothelin receptor type B (ETB). These receptors ... Lüscher TF, Barton M (November 2000). "Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel ... ETB receptors bind ETs and SRTXs with little selectivity whereas ETA receptors show greater affinity for ET-1, ET-2 and SRTX-b ... Sokolovsky M, Ambar I, Galron R (October 1992). "A novel subtype of endothelin receptors". The Journal of Biological Chemistry ...
These tumor-associated endothelial cells have been found to over-express the endothelin B receptor, which suppresses T-cell ... Kandalaft, Lana E.; Facciabene, Andrea; Buckanovich, Ron J.; Coukos, George (2009-07-15). "Endothelin B Receptor, a New Target ... "Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy". Nature Medicine ... Loss of pericyte growth factor (PDGFB) and its receptor on endothelial cells are molecular-level changes that can account for ...
Shraga-Levine Z, Sokolovsky M (2000). "Functional coupling of G proteins to endothelin receptors is ligand and receptor subtype ... AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U (2001). "The angiotensin II AT2 receptor is an AT1 receptor antagonist". J. ... 1996). "The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families ... Offermanns S, Simon MI (1995). "G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C". J. Biol. Chem ...
Bosentan belongs to a new class of drug and works by blocking endothelin receptors. It is specifically indicated only for the ... Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors. azilsartan candesartan ... Aldosterone receptor antagonists: eplerenone spironolactone Aldosterone receptor antagonists are not recommended as first-line ... On the other hand, β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists ...
"Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial ... Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However ... Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist (ERA) approved for the treatment of ... ET receptors are G protein coupled receptors and, when activated, lead to an increase in intracellular calcium levels via the G ...
This corresponds with receptor expression at the pharyngeal arches. Pharyngeal arch 3 expresses EphrinA and EphrinB1 receptors ... A second signalling pathway that directs crest cell movement are the family of endothelin ligands. Migrating cardiac neural ...
Constriction has been shown in vitro to occur when NE is placed in the synapse and is taken up by astrocyte receptors. NE ... The peptides angiotensin II and endothelin-1 (ET-1) bind to pericytes and are vasoactive. Endothelial cells induce expression ... It has also been shown that agonists of metabotropic glutamate receptors (mGluR) also increase intracellular Ca2+ to produce ... Pericytes have both cholinergic (α2) and adrenergic (β2) receptors. Stimulation of the latter leads to vessel relaxation, while ...
Endothelin receptor antagonist(英語:Endothelin receptor antagonist). *NK1 receptor antagonist(英語:NK1 receptor antagonist) ... Glutamate receptor antagonist(英語:Excitatory amino acid antagonist) (NMDA(英語:NMDA receptor antagonist)) ... Cannabinoid receptor antagonist(英語:Cannabinoid receptor antagonist). *Endocannabinoid enhancer(英語:Endocannabinoid enhancer) ( ... Glutamate receptor agonist(英語:Excitatory amino acid agonist) (AMPA(英語:Ampakine)) ...
transmembrane signaling receptor activity. • Wnt-activated receptor activity. • G-protein coupled receptor activity. ... "Frizzled Receptors: FZD5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... cell surface receptor signaling pathway. • vasculature development. • regulation of autophagy of mitochondrion. • branching ...
... mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial ... Grenader A, Healy DP (July 1991). "Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells". J. ... Hughes AD, Sever PS (1989). "Action of fenoldopam, a selective dopamine (DA1) receptor agonist, on isolated human arteries". ... D1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most ...
Receptors[edit]. Main article: Bradykinin receptor. *The B1 receptor (also called bradykinin receptor B1) is expressed only as ... The kinin B1 and B2 receptors belong to G protein coupled receptor (GPCR) family. ... This receptor has been also described to play a role in inflammation.[10] Most recently, it has been shown that the kinin B1 ... Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ...
taste receptor activity. • fatty acid binding. • lipid binding. • G-protein coupled receptor activity. ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... G-protein coupled receptor 120 is a protein that in humans is encoded by the GPR120 gene.[5][6] ... "Entrez Gene: GPR120 G protein-coupled receptor 120".. *^ Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, ...
Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ... Endothelin. *Agonists: Endothelin 1. *Endothelin 2. *Endothelin 3. *IRL-1620. *Sarafotoxin. *Antagonists: A-192621 ...
IGF-2 exerts its effects by binding to the IGF-1 receptor and to the short isoform of the insulin receptor (IR-A or exon 11-).[ ... 8] IGF2 may also bind to the IGF-2 receptor (also called the cation-independent mannose 6-phosphate receptor), which acts as a ... insulin receptor binding. • hormone activity. • GO:0001948 protein binding. • growth factor activity. • insulin-like growth ... Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ...
... are agonists of the prostacyclin receptor, which leads to vasodilation in the pulmonary circulation.[1] ...
Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ... It is a peptidomimetic consisting of ten amino acids, which is a selective and specific antagonist of bradykinin B2 receptors. ... Icatibant acts as a bradykinin inhibitor by blocking the binding of native bradykinin to the bradykinin B2 receptor. Little is ... These symptoms are mediated by activation of bradykinin B2 receptors. ...
G-protein coupled receptor signaling pathway. • signal transduction. • G-protein coupled purinergic nucleotide receptor ... G-protein coupled purinergic nucleotide receptor activity. • G-protein coupled receptor activity. • signal transducer activity ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... Probable G-protein coupled receptor 34 is a protein that in humans is encoded by the GPR34 gene.[5][6][7] ...
transmembrane-ephrin receptor activity. • protein binding. • ephrin receptor binding. Cellular component. • anchored component ... The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been ... Zhou R (1998). "The Eph family receptors and ligands". Pharmacol. Ther. 77 (3): 151-81. doi:10.1016/S0163-7258(97)00112-5. PMID ... Wilkinson DG (2001). "Multiple roles of EPH receptors and ephrins in neural development". Nat. Rev. Neurosci. 2 (3): 155-64. ...
Endothelin receptor type B. *STX17 (Gray). Category:Horse coat colors. Horse coat color ...
The adenosine receptors (or P1 receptors[1]) are a class of purinergic G protein-coupled receptors with adenosine as the ... A2A adenosine receptor[edit]. Main article: Adenosine A2A receptor. As with the A1, the A2A receptors are believed to play a ... A1 adenosine receptor[edit]. Main article: Adenosine A1 receptor. The adenosine A1 receptor has been found to be ubiquitous ... Adenosine receptors Receptor. Gene. Mechanism [15]. Effects. Agonists. Antagonists A1 ADORA1. Gi/o → cAMP↑/↓ *Inhibition *↓ ...
Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ... Léna I, Dh tel H, Garbay C, Daugé V (January 2001). "Involvement of D2 dopamine receptors in the opposing effects of two CCK-B ... Kalindjian SB, McDonald IM (2007). "Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligand". ... "Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor". Journal of Medicinal ...
... and endothelin receptor antagonists have no effect, and in some cases worsen of the EIPH. ...
Endothelin receptor type B. *STX17 (Gray). Category:Horse coat colors. Retrieved from "https://en.wikipedia.org/w/index.php? ...
Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ... Endothelin. *Agonists: Endothelin 1. *Endothelin 2. *Endothelin 3. *IRL-1620. *Antagonists: A-192621 ... Telcagepant (INN) (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational ... "Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine". Neurology. 70 (16): ...
"Prostanoid Receptors: EP3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... prostaglandin receptor activity. • signal transducer activity. • prostaglandin E receptor activity. • protein binding. ... Prostaglandin E2 receptor 4 (EP4). അവലംബം[തിരുത്തുക]. *↑ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000050628 - Ensembl, May ... "EP3-2 receptor mRNA expression is reduced and EP3-6 receptor mRNA expression is increased in gravid human myometrium". Journal ...
Endothelin. *Agonists: Endothelin 1. *Endothelin 2. *Endothelin 3. *IRL-1620. *Antagonists: A-192621 ... Galanin receptor 1 (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene.[5] ... "Galanin Receptors: GAL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it. *v ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... Following apoptosis, it is thought there is a massive degranulation of vasoconstrictors, including endothelins and free ...
endothelin. ↑endothelin receptor ETA. angiotensin II. ↑Angiotensin receptor 1 *On smooth muscle cells: Activation of Gq --, ↑ ... P2X receptor. ↑Ca2+. NPY. NPY receptor Activation of Gi --, ↓cAMP --, ↓PKA activity --, ↓phosphorylation of MLCK --, ↑MLCK ... α1 adrenergic receptor Activation of Gq --, ↑PLC activity --, ↑IP3 and DAG --, activation of IP3 receptor in SR --, ↑ ... Arginine vasopressin receptor 1 (V1) on smooth muscle cells Activation of Gq --, ↑PLC activity --, ↑IP3 and DAG --, activation ...
Taste receptor 2 member 38 is a protein that in humans is encoded by the TAS2R38 gene. TAS2R38 is a bitter taste receptor; ... G-protein coupled receptor activity. • signal transducer activity. • bitter taste receptor activity. ... TAS2R38, PTC, T2R38, T2R61, taste 2 receptor member 38, THIOT. External IDs. OMIM: 607751 MGI: 2681306 HomoloGene: 47976 ... Fischer A, Gilad Y, Man O, Pääbo S (2005). "Evolution of bitter taste receptors in humans and apes". Mol. Biol. Evol. 22 (3): ...
epidermal growth factor receptor binding. • ربط بروتيني. • growth factor activity. • protein tyrosine kinase activity. • ... "Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin.". ... epidermal growth factor receptor signaling pathway. • peptidyl-tyrosine phosphorylation. • phosphatidylinositol phosphorylation ... positive regulation of epidermal growth factor-activated receptor activity. • تمايز خلوي. • positive regulation of cytokine ...
Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 ... Vincent JP (October 1995). "Neurotensin receptors: binding properties, transduction pathways, and structure". Cellular and ... Endothelin. *Agonists: Endothelin 1. *Endothelin 2. *Endothelin 3. *IRL-1620. *Sarafotoxin. *Antagonists: A-192621 ...
leukotriene receptor activity. • cysteinyl leukotriene receptor activity. • galanin receptor activity. Cellular component. • ... "Leukotriene Receptors: CysLT2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes# ... G-protein coupled peptide receptor activity. • signal transducer activity. • G-protein coupled receptor activity. • ...
Endothelin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.. ... Update on endothelin receptor nomenclature". Pharmacol. Rev. 54 (2): 219-26. PMID 12037137. doi:10.1124/pr.54.2.219.. ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A ... Ovaj receptor ima udela u ABCD sindromu[2] i nekim formama Vardenburgovog sindroma.[3] ...
The bombesin receptors are a group of G-protein coupled receptors which bind bombesin.. Three bombesin receptors are currently ... BB1, previously known as Neuromedin B receptor NMBR. BB2, previously known as Gastrin-releasing peptide receptor GRPR. BB3, ... previously known as Bombesin-like receptor 3 BRS3. External links[edit]. *. "Bombesin Receptors". IUPHAR Database of Receptors ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
adenylate cyclase-activating G-protein coupled receptor signaling pathway. • G-protein coupled receptor signaling pathway. • ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ... G-protein coupled receptor activity. Cellular component. • plasma membrane. • membrane. • integral component of membrane. • ... Probable G-protein coupled receptor 26 is a protein that in humans is encoded by the GPR26 gene.[5] ...
mineralocorticoid receptor activity. • steroid binding. • G-protein coupled receptor activity. • steroid hormone receptor ... Receptor/signaling modulators. Estrogens and antiestrogens. Androgen receptor modulators. Progesterone receptor modulators. ... G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans ... "Estrogen (G protein coupled) Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ...
Retrieved from "https://en.wikipedia.org/w/index.php?title=Talk:Endothelin_receptor_antagonist&oldid=814273153" ...
Endothelin receptor eta; Endothelin receptor type A; Endothelin type A receptor; Endothelin-A receptor; ETA; ETA receptor; ETA ... A-type endothelin receptor; EDNRA; Endothelin receptor eta; Endothelin receptor type A; Endothelin type A receptor; Endothelin- ... A receptor; ETA; ETA receptor; ETA type endothelin receptor; ETAR; ETA-R; ETR; ETR ETA; ETRA; Type A endothelin receptor ... Quantification of endothelin receptor subtypes in peripheral tissues reveals downregulation of ET(A) receptors in ET(B)- ...
... to its receptors on smooth muscle cells which results in vasodilation. Endothelin receptors are relatively enriched in ... Three endothelin receptor antagonists are currently approved and in use in the United States: bosentan (2001: Tracleer), ... While all endothelin receptor antagonists have been associated with occasional transient serum enzyme elevations during therapy ... In patients with pulmonary arterial hypertension, (PAH) the endothelin receptor antagonists have been shown to improve exercise ...
There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose ... 2016) Endothelin Pharmacol. Rev. 68: 357-418. pmid =26956245 doi =10.1124/pr.115.011833 "Endothelin Receptors". IUPHAR ... Endothelin receptor antagonist Walter F. Boron, Emile L. Boulpaep, eds. (2009). Medical physiology a cellular and molecular ... Update on endothelin receptor nomenclature". Pharmacol. Rev. 54 (2): 219-26. CiteSeerX 10.1.1.546.8632. doi:10.1124/pr.54.2.219 ...
Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB ... G protein-coupled receptor, rhodopsin-like (IPR000276) *Endothelin receptor family (IPR000499) *Endothelin receptor A ( ... presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors.. J. Clin. Endocrinol. ... Endothelins.. FASEB J. 5 2713-20 1991. Maguire JJ, Davenport AP. ETA receptor-mediated constrictor responses to endothelin ...
An endothelin receptor antagonist (ERA) is a drug that blocks endothelin receptors. Three main kinds of ERAs exist: selective ... Edonentan is an endothelin receptor antagonist drug. Endothelin receptor antagonists v t e. ... which affect both endothelin A and B receptors. selective ETB receptor antagonists (BQ-788 and A192621) which affect endothelin ... ETA receptor antagonists (sitaxentan, ambrisentan, atrasentan, BQ-123, zibotentan), which affect endothelin A receptors. dual ...
Expression of endothelin-1, endothelin-converting enzyme and endothelin receptors in chronic heart failure. Circulation. 1999; ... Endothelin-1 potentiates human smooth muscle cell growth to PDGF: effects of ETA and ETB receptor blockade. Circulation. 1999; ... Clearance of circulations endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun. 1994; 199: 1461-1465. ... Endothelin B receptor-mediated contraction in human pulmonary resistance arteries. Br J Pharmacol. 1996; 119: 1125-1130. ...
The present invention relates to new pyridine sulfonamide modulators of endothelin-A receptor, pharmaceutical compositions ... The term "endothelin-A receptor" refers to a subtype of receptor which binds endothelins. Endothelins are a family of three 21- ... In particular, an endothelin-A receptor-mediated disorder is one in which modulation of endothelin-A receptor results in some ... An endothelin-A receptor-mediated disorder may be completely or partially mediated by modulating endothelin-A receptor. ...
Buy our Endothelin B Receptor peptide. Ab109654 is a blocking peptide for ab95911 and has been validated in BL. Abcam provides ... Endothelin B Receptor peptide. See all Endothelin B Receptor proteins and peptides. ... Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRB sub-subfamily. ... Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a ...
Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism.. Tsang JY1, Lamm WJ, ... We concluded that endothelin antagonism had minimal impact on gas exchange following APTE and confirmed our earlier observation ... We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute ... pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. Nine anesthetized piglets ( ...
cell surface receptor signaling pathway / endothelin receptor signaling pathway / enteric nervous system development / enteric ... Tsutsumi M, Liang G, Jones PA: Novel endothelin B receptor transcripts with the potential of generating a new receptor. Gene. ... Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ... Attie T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S: Mutation of the endothelin-receptor B gene in ...
Endothelin-1 receptor. P25101. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. Pharmacological action? ... Endothelin-1 receptor. Kind. protein. Organism. Human. Polypeptides. Name. UniProt ID. ...
There are no specific protocols for Recombinant Human Endothelin B Receptor protein (ab114259). Please download our general ...
It is synthesized and released from endothelial cells and acts upon two receptor subtypes designated as ETA and ETB. In this ... Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. ... Receptor, Endothelin A. Receptor, Endothelin B. Receptors, Endothelin / antagonists & inhibitors*, metabolism. Sulfonamides / ... 0/Dipeptides; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Receptors, Endothelin; 0/Sulfonamides ...
Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation ... The endothelin type A receptor (ETAR) is a G-protein coupled receptor (GPCRs) expressed on both non-immune (e.g., endothelial ... Teoh, J. et al. Endothelin-1/endothelin A receptor-mediated biased signaling is a new player in modulating human ovarian cancer ... Asham, E. et al. Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism. Br. J ...
Endothelin B Receptor Polyclonal Antibody from Invitrogen for Western Blot and Immunohistochemistry (Paraffin) applications. ... Endothelin B receptor; Endothelin receptor non-selective type; endothelin receptor subtype B1; endothelin-B receptor; ET-B; ET- ... endothelin receptor activity. protein binding. peptide hormone binding. type 1 angiotensin receptor binding. receptor activity ... Cite Endothelin B Receptor Polyclonal Antibody. The following antibody was used in this experiment: Endothelin B Receptor ...
"Endothelin Receptors: ETB". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger ... Endothelin receptor type B, also known as ETB is a protein that in humans is encoded by the EDNRB gene.[1] ... Endothelin receptor. References. *↑ Cyr C, Huebner K, Druck T, Kris R (Nov 1991). "Cloning and chromosomal localization of a ...
PRR KO mice had greatly increased IMCD ETA receptor mRNA and protein, while ETB mRNA and protein were decreased. Water loaded ... and prorenin/renin/prorenin receptor (PRR) systems have opposing physiological effects on collecting duct (CD) salt and water ... Nephron prorenin receptor deficiency alters renal medullary endothelin-1 and endothelin receptor expression The endothelin (ET ... and prorenin/renin/prorenin receptor (PRR) systems have opposing physiological effects on collecting duct (CD) salt and water ...
Find Endothelin Receptors research area related information and Endothelin Receptors research products from R&D Systems. Learn ... Endothelin Receptors. EDNRA and EDNRB (endothelin A and B receptors, respectively) are members of the rhodopsin-like 7- ... transmembrane receptor family. EDNRA binds endothelins ET-1 and ET-2 preferentially, and is expressed on vascular smooth muscle ... EDNRB binds all three endothelin forms equally, and is expressed on endothelial cells where it mediates vasodilation. ...
Endothelin Receptor (ET) Antagonists Overview. Endothelin Receptor (ET) Antagonists Disease Associated. Endothelin Receptor (ET ... Endothelin Receptor (ET) Antagonists Phase II Products. Comparative Analysis. Endothelin Receptor (ET) Antagonists Phase I and ... Endothelin Receptor (ET) Antagonists Assessment by Molecule Type. Endothelin Receptor (ET) Antagonists Assessment by Stage and ... Endothelin Receptor (ET) Antagonists Assessment by Molecule Type. Endothelin Receptor (ET) Antagonists Assessment by Stage and ...
In contrast to endothelin-1 (ET-1) and several of its analogues, sarafotoxin S6c (S6c) was a much more potent inhibitor of [ ... Sarafotoxin S6c: an agonist which distinguishes between endothelin receptor subtypes Biochem Biophys Res Commun. 1991 Mar 15; ... In contrast to endothelin-1 (ET-1) and several of its analogues, sarafotoxin S6c (S6c) was a much more potent inhibitor of [ ... suggesting the existence of ET-1 receptor subtypes (aorta/atria, ETA; hippocampus/cerebellum, ETB). S6c was a potent activator ...
Endothelin Receptor Antagonists for the Treatment of Raynauds Phenomenon and Digital Ulcers in Systemic Sclerosis. Kait ... The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor ... Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic ...
... Clin Pharmacol ... Introduction: Bosentan (Ro 47-0203) is a potent and mixed ETA-and ETB-receptor antagonist. Its activity has been studied in a ... At regular intervals, blood pressure, pulse rate, and skin responses to intradermally injected endothelin-1 (ET-1) were ...
Endothelin-1 Induces an Endothelin-A-Receptor-Dependent and L-NAME-Sensitive Vasoconstriction in the Isolated Perfused Guinea- ... and ETB-receptors in the eicosanoid-releasing properties of endothelin-1 (ET-1) in the guinea-pig perfused lung. More recently ... In this study we investigate the contribution of both ET receptors as well as of the eicosanoids and nitric oxide to the ... Indomethacin (5 μM) and the ETB-receptor antagonist, BQ-788 (10 nM) did not affect the constrictor effect of ET-1. The infusion ...
Interaction of endothelin-3 with endothelin B receptor is essential for development of epidermal melanocytes and enteric ... Chakravarti A (1996) Endothelin receptor mediated signaling in Hirschsprung disease. Hum Mol Genet 5, 303-307PubMedGoogle ... Attie T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S (1995) Mutation of the endothelin-receptor B gene ... Ceccherini I, Zhang A, Matera I, Yang G, Devoto M, Romeo G, Cass D (1995) Interstitial deletion of the endothelin-B receptor ...
Isolation of Human Cardiac Endothelin Receptors by a Peptide-Receptor Mobility Shift Assay Clin Sci (Lond) (August,1993) ... Endothelin Peptides and Receptors in Human Kidney Fiona E. Karet Fiona E. Karet ... Fiona E. Karet; Endothelin Peptides and Receptors in Human Kidney. Clin Sci (Lond) 1 September 1996; 91 (3): 267-273. doi: ... Endothelin type B (ET B ) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD ...
IL-15-induced hypernociception was inhibited by treatment with a dual endothelin receptor type A (ET(A))/endothelin receptor ... Synonyms: ET-A, ET-AR, ETa, Endothelin A receptor, Endothelin-1 receptor, ... ... Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of ... Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice. Nakamura, T., Ebihara, I., ...
Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple ... Endothelin A receptor antagonism and angiotensin-converting enzyme inhibition are synergistic via an endothelin B receptor- ... Endothelin A receptor antagonism and angiotensin-converting enzyme inhibition are synergistic via an endothelin B receptor- ... Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. Guruli, G., Pflug, B.R ...
A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels. ... Receptor, Endothelin B; Endothelin B-2 Receptors; Endothelin B 2 Receptor; Endothelin B 2 Receptors; Receptor, Endothelin B-2; ... Receptors, Endothelin B; Receptors, Endothelin B-2; Endothelin B Receptors; Endothelin B-2 Receptor; Receptor, Endothelin B, ... Endothelin B Receptor. Subscribe to New Research on Endothelin B Receptor A subtype of endothelin receptor found predominantly ...
Antibodies for proteins involved in endothelin A receptor binding pathways, according to their Panther/Gene Ontology ... Antibodies for proteins involved in endothelin A receptor binding pathways; according to their Panther/Gene Ontology ...
  • Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide (see structure in Table 1 ) that was first isolated and identified in 1988 from porcine aortic endothelial cells. (springer.com)
  • The ETA receptor is found predominantly on smooth muscle cells, whereas the ETB receptor is present on both smooth muscle and vascular endothelial cells. (nih.gov)
  • ETA and ETB receptors are both widely distributed, ETA receptors are mainly located on vascular smooth muscle cells, whereas ETB receptors are present on endothelial cells lining the vessel wall. (ebi.ac.uk)
  • ET B receptors are localized on endothelial cells and, to some extent, smooth muscle cells and macrophages. (ahajournals.org)
  • In normal states, it appears that stimulation of the ET A receptor on the smooth muscle cell causes vasoconstriction and mitogenic effects that are opposed by stimulation of the ET B receptor on the endothelial cell (see Figure 1 ). (ahajournals.org)
  • 24 There could also be underexpression of the ET B receptor on the endothelial cell. (ahajournals.org)
  • The interaction between ET-1 on endothelial and smooth muscle cells, and the ET A and ET B receptors is shown. (ahajournals.org)
  • Arai H, Nakao K, Hosoda K, Ogawa Y, Nakagawa O, Komatsu Y, Imura H: [Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells]. (drugbank.ca)
  • It is synthesized and released from endothelial cells and acts upon two receptor subtypes designated as ETA and ETB. (biomedsearch.com)
  • EDNRB binds all three endothelin forms equally, and is expressed on endothelial cells where it mediates vasodilation. (rndsystems.com)
  • We have published in this journal a study investigating comprehensively the vascular responses in a mouse model of heterozygous endothelial overexpression of the endothelin-1 gene concluding that the latter in combination with obesity aggravates renal arterial dysfunction 1 . (nature.com)
  • By contrast to the similarly low plasma peptide levels in lean and obese wild type mice and littermates with heterozygous endothelial over-expression of the prepro-endothelin-1 gene (TET het ) 1 on standard chow or high fat diet, endothelin-1 levels in the lungs were significantly higher ( Figure 1A ). (nature.com)
  • Endothelin-1 (ET-1) content in lungs [ n =5-12, as picograms per milligram (pg/mg) lung tissue] (A) of wild-type (WT) mice and littermates with heterozygous endothelial overexpression of the endothelin-1 gene (TET het ) on standard chow (lean) and after 30 weeks of high fat feeding (obese). (nature.com)
  • By contrast, activation of endothelial ET B -receptors promotes the generation of nitric oxide, which thus leads to inhibition of contraction and facilitated relaxation 2 . (nature.com)
  • Such an up-regulation of the ET B -receptor pathway in the lungs, a tissue of high endothelial cell content, would support the decreased pulmonary tissue endothelin-1 levels observed in obese mice as a likely consequence of an accelerated clearance 6 . (nature.com)
  • 2 3 Of the endothelin family, endothelin-1 (ET-1) is produced by endothelial cells and may act on underlying smooth muscle cells, which bear endothelin type A (ET A ) and endothelin type B (ET B ) receptors. (ahajournals.org)
  • 5 Endothelins also interact with endothelial ET B receptors, which induce the generation of endothelium-derived nitric oxide and prostacyclin. (ahajournals.org)
  • In conclusion, the dual ETA/ETB receptor antagonist bosentan preserved endothelial and cardiac contractile function during ischemia and reperfusion via a mechanism dependent on endothelial NO production. (unboundmedicine.com)
  • Endothelin is produced by vascular endothelial cells and has potent vasoconstrictor effects 2 . (ersjournals.com)
  • A gene on chromosome 4q31.22 that encodes endothelin-A receptor, a member of the endothelin receptor group of G-protein-coupled receptors, located primarily in the vascular endothelial cells where they play a role in vasoconstriction, vasodilation, bronchoconstriction and cell proliferation. (thefreedictionary.com)
  • More than 20 years ago, endothelin-1 (ET-1) was isolated from aortic endothelial cells and found to have potent vasoconstrictive activity ( 3 ). (aacrjournals.org)
  • Endothelin (ET)-1, a potent vasoconstrictor peptide from vascular endothelial cells, 6 is also synthesized and secreted by cardiomyocytes 6 and induces hypertrophy of cardiomyocytes 6,7 through activating phospholipase C, protein kinase C, extracellular signal-regulated kinase (ERK) 1 and ERK2, and upregulation of c-Fos and c-Jun. (ahajournals.org)
  • Abstract The coronary vasoconstrictor effects of endothelins, mediated by both endothelin ETA and ETB receptors, may be differentially altered in pathophysiological states associated with endothelial dysfunction and elevated endothelin levels. (ahajournals.org)
  • Experimental hypercholesterolemia is associated with coronary endothelial dysfunction and increased circulating endothelin concentrations. (ahajournals.org)
  • 3,4 The two receptor subtypes have distinct tissue distribution and affinity to endothelin isoforms: ETA receptors are present on vascular smooth muscle cells, whereas ETB receptors are found on both vascular smooth muscle and endothelial cells. (ahajournals.org)
  • In pathophysiological conditions associated with endothelial dysfunction, such as hypercholesterolemia and heart failure, the vasomotor response of vessels to endothelins may be significantly altered. (ahajournals.org)
  • We have previously demonstrated that inhibition of endogenous endothelium-derived relaxing factor in vivo, mimicking pathophysiological states associated with endothelial dysfunction, results in an enhanced coronary microvessel vasoconstrictor response to ETB-receptor stimulation. (ahajournals.org)
  • Purpose: The objective of the study was to determine whether astrocytes and brain endothelial cells protect glioma cells from temozolomide (TMZ) through an endothelin-dependent signaling mechanism and to examine the therapeutic efficacy of the dual endothelin receptor antagonist, macitentan, in orthotopic models of human glioblastoma. (aacrjournals.org)
  • Experimental Design: We evaluated several endothelin receptor antagonists for their ability to inhibit astrocyte- and brain endothelial cell-induced protection of glioma cells from TMZ in chemoprotection assays. (aacrjournals.org)
  • Results: Only dual endothelin receptor antagonism abolished astrocyte- and brain endothelial cell-mediated protection of glioma cells from TMZ. (aacrjournals.org)
  • This is exemplified by studies showing that the blockade of ET receptors or ET-converting enzyme (ECE) activity in brain endothelial cells and glia, which results in endothelial hyperpermeability and cerebral vasoconstriction, reduces leukocyte infiltration into the injured spinal cord, which is associated with significant recovery of motor and neurological functions following SCI ( 16 - 18 ). (spandidos-publications.com)
  • The decrease in tumour blood flow and an increase in vascular resistance suggest that the vascular component of ETB receptors in the P22 tumour is localised on contractile elements rather than on endothelial cells. (whiterose.ac.uk)
  • Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. (ahajournals.org)
  • Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism. (nih.gov)
  • The purpose of this study will be to determine if blockade of endothelin 1 signalling via endothelin receptor A using ambrisentan or dual blockade (A&B) via bosentan can provide protection against methacholine induced bronchoconstriction in asthma. (clinicaltrials.gov)
  • Blockade of the endothelin system may thereby protect against airway narrowing. (clinicaltrials.gov)
  • The investigators will endeavour to examine the potential role of endothelin 1 in the development of airway narrowing in asthma through blockade of the endothelin receptors A&B through the use of bosentan and ambrisentan. (clinicaltrials.gov)
  • Endothelin receptor blockade prevents augmented extracellular matrix component mRNA expression and capillary basement membrane thickening in the retina of diabetic and galactose-fed rats. (diabetesjournals.org)
  • To explore the morphological and functional effect of selective and non-selective endothelin (ET)-receptor blockade in coronary artery disease (CAD). (bmj.com)
  • We found a broad variety of individual haemodynamic responses to ET-receptor antagonists with an overall neutral effect after an infusion period of 30 minutes despite an overall effective blockade of ET-receptors. (bmj.com)
  • the ET system is complex with a converting enzyme and two receptors, ET A -R and ET B -R. The receptors offer an opportunity for selective blockade. (asnjournals.org)
  • In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. (spandidos-publications.com)
  • We also examined the post‑traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. (spandidos-publications.com)
  • Whereas ET A -receptor blockade significantly increased the response to ET-1 in unaffected horses, ET B -receptor blockade significantly decreased the response in affected horses. (elsevier.com)
  • Furthermore, blockade of ETA or activation of ETB receptors significantly reduced intrarenal hypoxia in the diabetic kidney. (dissertations.se)
  • These results demonstrate involvement of ETA receptor signaling in diabetes-induced intrarenal hypoxia and ETA blockade or ETB activation might provide new therapeutical targets to reduce kidney hypoxia and disease progression in diabetes. (dissertations.se)
  • 1997. ETB receptor and nitric oxide synthase blockade induce BQ-123-sensitive pressor effects in the rabbit. (koreascience.or.kr)
  • 1996. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. (koreascience.or.kr)
  • Quantification of endothelin receptor subtypes in peripheral tissues reveals downregulation of ET(A) receptors in ET(B)-deficient mice. (springer.com)
  • Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB) [ PMID: 12037137 , PMID: 1719979 , PMID: 1849646 , PMID: 1710450 ], and are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (GPCRA) which stimulate multiple effectors via several types of G protein [ PMID: 7882989 ]. (ebi.ac.uk)
  • Endothelin-1 acts via two distinct receptor subtypes [endothelin-A (ET A ) and endothelin-B (ET B )] mediating the characteristic vasoconstrictor response upon activation by the peptide of vascular smooth muscle cells 2 . (nature.com)
  • Orally acting ET antagonists appear very promising in clinical trials, particularly in patients with chronic heart failure and hypertension, but more information on the roles of the ET receptor subtypes in health and disease is required so that an informed choice can be made between the use of endothelin-A (ET-A) receptor-selective and nonselective receptor antagonists. (springer.com)
  • Karet F, Kuc R, Davenport A. Novel ligands BQ 123 and BQ 3020 characterise endothelin receptor subtypes ETA and ETB in human kidney. (springer.com)
  • 4 Both receptor subtypes may mediate the vasoconstrictor effects of endothelins. (ahajournals.org)
  • However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. (unboundmedicine.com)
  • We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. (unboundmedicine.com)
  • Endothelin1 (ET-1), a 21-amino acid vasoconstrictor peptide, has been implicated in a range of pathophysiological processes, such as vasoconstrictor tone, humoral homeostasis, neurotransmission, oxidative stress, inflammation and ER stress, which is mediated mainly through two G-protein coupled receptor subtypes, endothelin subtype A receptor (ETAR) and endothelin subtype B receptor (ETBR). (dovepress.com)
  • 90% of ET receptors in cardiomyocytes are of the ET A subtype, whereas fibroblasts had a nearly equal proportion of the ET A and ET B subtypes. (ahajournals.org)
  • 12 13 14 15 16 Two receptor subtypes (ET A and ET B ) are well identified. (ahajournals.org)
  • However, little information on the cellular distribution and regulation of cardiac ET-1 receptor subtypes is available. (ahajournals.org)
  • Previous studies have reported the existence of at least two subtypes of Ang II cell surface receptors (AT 1 and AT 2 ) in various peripheral tissues as well as in the brain. (ahajournals.org)
  • Selective endothelin-a receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. (springer.com)
  • ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. (ahajournals.org)
  • We concluded that endothelin antagonism had minimal impact on gas exchange following APTE and confirmed our earlier observation that the main mechanism for hypoxemia in APTE was due to the mechanical redistribution of pulmonary regional blood flow away from the embolized vessels, resulting in the creation of many divergent low and high Va/Q regions. (nih.gov)
  • These results suggest that although CGS 31398 is a potent dual inhibitor of ETA/ETB receptor binding, it surprisingly displays potent ETB and weak ETA receptor antagonism in functional assays. (biomedsearch.com)
  • Endothelin receptor antagonism during preeclampsia: a matter of timing? (portlandpress.com)
  • Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. (unboundmedicine.com)
  • VL - 286 IS - 5 N2 - Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. (unboundmedicine.com)
  • Previous studies have shown that both the pulmonary and systemic circulation are improved by combined endothelinA- and endothelinB-receptor antagonism. (ersjournals.com)
  • Long-term studies in patients with symptomatic heart failure were conducted (Research on Endothelin Antagonism in Chronic Heart Failure (REACH) and Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure (ENABLE)), but these trials were prematurely stopped, due to unexpected increases of adverse events, without improvements in clinical status 10 - 12 . (ersjournals.com)
  • They therefore represent a novel therapeutic target: specific receptor dual antagonism may prove beneficial in disease management. (umontreal.ca)
  • 2003. Acute endothelin A receptor antagonism improves pulmonary arterial hypertension that is primary or autoimmune and related to congenital heart disease. (koreascience.or.kr)
  • Three endothelin receptor antagonists are currently approved and in use in the United States: bosentan (2001: Tracleer), ambrisentan (2007: Letairis) and macitentan (2013: Opsumit). (nih.gov)
  • While all endothelin receptor antagonists have been associated with occasional transient serum enzyme elevations during therapy, only bosentan and sitaxentan have been clearly linked to instances of clinically apparent, acute liver injury. (nih.gov)
  • The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. (nih.gov)
  • The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. (ahajournals.org)
  • Bosentan (Ro 47-0203) is a potent and mixed ETA-and ETB-receptor antagonist. (nih.gov)
  • Two receptors exist for endothelin 1, Endothelin A & B. Both can be blocked by Bosentan, and the A receptor by ambrisentan. (clinicaltrials.gov)
  • Treatment with the combined endothelin type A/endothelin type B receptor antagonist bosentan moderately reduced blood pressure rise and nearly completely blunted the development of vascular hypertrophy, particularly in small arteries, in the deoxycorticosterone acetate-salt hypertensive model, suggesting a paracrine role for vascular endothelin-1 in the induction of blood vessel hypertrophy in some forms of experimental hypertension. (ahajournals.org)
  • Chronic treatment of DOCA-salt hypertensive rats with the new combined ET A /ET B receptor antagonist bosentan resulted in a reduced rise in blood pressure associated with attenuation of vascular hypertrophy, particularly at the level of mesenteric small arteries, where the normalization of structure exceeded what could be expected from the slightly lower blood pressure reached. (ahajournals.org)
  • 13 14 15 16 To determine whether there was a relationship between the response of blood pressure and that of vascular hypertrophy and remodeling to treatment with the combined ET A /ET B receptor antagonist bosentan in SHR, we designed this study in which SHR and WKY were treated chronically with bosentan. (ahajournals.org)
  • Bosentan is a dual endothelin A and B receptor antagonist for treatment of pulmonary arterial hypertension. (medscape.com)
  • Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. (unboundmedicine.com)
  • Motivated by these pathophysiological and epidemiological insights, drugs such as bosentan, an oral nonselective endothelin receptor antagonist, were developed that could interfere and reduce the effects of the endothelin system. (ersjournals.com)
  • Simultaneously, similar animal groups were treated with a general ET receptor blocker (bosentan, 100 mg x kg(-1) x day(-1)) and investigated. (diabetesjournals.org)
  • Salicylates potentiate relaxing actions of receptor antagonists such as bosentan. (aspetjournals.org)
  • Endothelin receptor type B , also known as ET B is a protein that in humans is encoded by the EDNRB gene . (wikidoc.org)
  • EDNRA and EDNRB (endothelin A and B receptors, respectively) are members of the rhodopsin-like 7-transmembrane receptor family. (rndsystems.com)
  • Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. (springer.com)
  • Endothelin B Receptor antibody detects Ednrb protein at membrane on U87 xenograft by immunohistochemical analysis. (genetex.com)
  • The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca 2+ ]. (jci.org)
  • Endothelin B Receptor antibody LS-A105985 is a biotin-conjugated rabbit polyclonal antibody to Endothelin B Receptor (EDNRB ) from human, mouse, rat and other species. (lsbio.com)
  • ET-1 acts by engagement of cell surface receptors that result in activation of intracellular pathways leading to vasoconstriction and proliferation of smooth muscle cells. (nih.gov)
  • ETA receptors are considered to be the primary vasoconstrictor and growth-promoting receptor, and the binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure [ PMID: 1351106 ]. (ebi.ac.uk)
  • ETA is a subtype for vasoconstriction These receptors are found in the smooth muscle tissue of blood vessels, and binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure. (wikipedia.org)
  • 21 When stimulated, the ET A receptors induce vasoconstriction and cellular proliferation by increasing intracellular calcium. (ahajournals.org)
  • EDNRA binds endothelins ET-1 and ET-2 preferentially, and is expressed on vascular smooth muscle where it mediates vasoconstriction. (rndsystems.com)
  • To determine whether big-endothelin-1 (big-ET-1)-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123. (jci.org)
  • CGS 27830 (100 mcg/min for 10 min), an ET-A and -B receptor antagonist, did not change basal tone but blocked big-ET-1-induced pulmonary vasoconstriction. (jci.org)
  • Angiotensin II enhances endothelin-1-induced vasoconstriction through upregulating endothelin type A receptor. (genetex.com)
  • EDNRA encodes the bovine protein Endothelin-1 receptor (ETA), a peptide that plays a role in potent and long-lasting vasoconstriction. (cellsciences.com)
  • The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. (physiology.org)
  • These studies demonstrate that experimental hypercholesterolemia is characterized by enhanced coronary vasoconstriction to endothelins in vitro, the mechanism of which is mediated mainly through the ETB receptor. (ahajournals.org)
  • 4 Endothelin binding to vascular smooth muscle ETA and ETB receptors mediates vasoconstriction, whereas ETB receptors on the vascular endothelium mediate a vasodilator response, presumably through increased production and release of nitric oxide and/or prostacyclin 6 and activation of potassium channels. (ahajournals.org)
  • Endothelins mediate vasoconstriction of noncoronary resistance and capacitance arteries through both ETA and ETB receptors. (ahajournals.org)
  • 7-10 The relative contribution made by each receptor to endothelin-mediated vasoconstriction is different between the two vessel types. (ahajournals.org)
  • 10 Endothelin at pathophysiological concentrations also causes coronary vasoconstriction through stimulation of both types of receptors. (ahajournals.org)
  • 2,11-14 It has been suggested that the relative contribution of each receptor to endothelin-mediated vasoconstriction is different in canine conduit and resistance coronary arteries, in similarity with noncoronary arteries. (ahajournals.org)
  • Vasoconstriction occurred uniformly throughout the P22 tumour mass, consistent with a measured homogeneous distribution of ETB receptors. (whiterose.ac.uk)
  • In normal physiology, endothelin 1 binding to endothelin receptor type A (ETA) induces vasoconstriction, which can be blocked by the specific ETA antagonist BQ123, whereas endothelin 1 binding to endothelin receptor type B (ETB) induces nitric oxide-dependent vasodilation. (dissertations.se)
  • ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. (ebi.ac.uk)
  • Endothelin peptides and the kidney. (ebi.ac.uk)
  • Its ligand, endothelin , consists of a family of three potent vasoactive peptides: ET 1 , ET 2 , and ET 3 . (wikidoc.org)
  • These studies therefore aimed to characterize endothelin peptides and receptors ET A and ET B in human kidney, to direct potential therapeutic endeavours. (portlandpress.com)
  • ET s were originally isolated from porcine aortic endothelium [1], but subsequent investigations revealed that these peptides are synthesized and their receptors are expressed in a great variety of tissues and organs, where they play important physiological and pathophysiological roles [2-6]. (springer.com)
  • 1996 The endothelin peptides. (springer.com)
  • The endothelin system of peptides and their receptors have been implicated for their neurodegenerative role in glaucoma. (arvojournals.org)
  • Endothelins (ETs) are potent vasoconstrictive peptides that are secreted by the vascular endothelium and other tissues in vertebrates. (biologists.org)
  • Endothelins (ETs) are a family of vasoactive peptides that have mitogenic properties and have also been associated with altered long-term nuclear signaling. (diabetesjournals.org)
  • Endothelins are 21 amino acid peptides that act as modulators of coronary vasomotor tone. (ahajournals.org)
  • It has the same affinity at the ET B receptor as ET-1 but, at physiological concentrations, has little or no affinity for the ET A . The only endogenous peptides with a high degree of sequence similarity to the ETs are the sarafotoxins (S6a, S6b, S6c, S6d). (guidetopharmacology.org)
  • Edn1 is one of three known Endothelin peptides, each synthesized as a larger prepropeptide and subsequently modified by furin proteases and endothelin converting enzymes (ECEs) to form a mature ligand. (biologists.org)
  • The ET system consists of two G-protein-coupled receptors (ET receptors A and B, ETRs), three peptides (ET-1, ET-2 and ET-3), and two activating peptidases (ECE-1 and ECE-2). (spandidos-publications.com)
  • Role of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. (springer.com)
  • Endothelin receptors are relatively enriched in pulmonary vasculature and their inibition results in a decrease in pulmonary vascular pressure. (nih.gov)
  • In patients with pulmonary arterial hypertension, (PAH) the endothelin receptor antagonists have been shown to improve exercise tolerance and slow progression of disease. (nih.gov)
  • The use of endothelin receptor antagonists in pulmonary arterial hypertension (PAH) is based upon the proposed pathogenesis of this disease, which is marked by enhanced synthesis of ET-1 and progressive proliferation and hypertrophy of smooth muscle cells in the pulmonary vasculature. (nih.gov)
  • In several randomized controlled trials, endothelin receptor antagonists were shown to decrease pulmonary vascular pressure and improve exercise tolerance and symptoms in patients with PAH. (nih.gov)
  • The selective ET A receptor antagonist sitaxsentan also improves hemodynamics and exercise capacity in patients with pulmonary arterial hypertension. (ahajournals.org)
  • We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. (nih.gov)
  • and 3) selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS, and heme oxygenase 1 are potential mechanisms of protection against hypoxic pulmonary hypertension in the CBDL-CH rats. (curehunter.com)
  • Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation. (jci.org)
  • To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs. (jci.org)
  • and (c) ET-B receptor stimulation causes pulmonary vasodilation through EDNO release. (jci.org)
  • These findings support the hypothesis that endothelin may play a role in modulation of high basal pulmonary vascular resistance in the normal fetus. (jci.org)
  • Ambrisentan is an endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with World Health Organization (WHO) class II or III symptoms. (medscape.com)
  • Furthermore, the change in pulmonary circulation seen in the present shock model is to a large extent mediated by the endothelinA-receptor mechanism. (ersjournals.com)
  • Their findings, therefore, challenge the pathophysiological rationale for the use of endothelin receptor antagonists in heart failure with secondary pulmonary hypertension. (ersjournals.com)
  • Derek's extensive background in launching new drugs, including pre-launch work on Zetia(R) and Clarinex(R), will be invaluable as we drive towards commercialization of sitaxsentan, our once daily, selective endothelin A receptor antagonist for the treatment of pulmonary arterial hypertension. (thefreedictionary.com)
  • a partnership formed by ICOS Corporation (Nasdaq:ICOS) and Texas Biotechnology Corporation (AMEX:TXB), announced that patients are being recruited for the STRIDE (Sitaxsentan To Relieve ImpaireD Exercise in pulmonary hypertension) Trial, a pivotal Phase 2/3 study with sitaxsentan, an oral endothelin A receptor antagonist. (thefreedictionary.com)
  • Background Endothelin-1 type A receptor (ETAR) antagonists (e.g. ambrisentan) are currently approved by the U.S Food and Drug administration, representing a well-tolerated treatment of pulmonary arterial hypertension (PAH)[1] for patients with connective tissue diseases such as systemic sclerosis (SSc). (bmj.com)
  • The higher level of serum Endothelin and expression of ET-1 and ETA in broiler lungs may explain the higher sensitivity of broilers to the vasoconstrictions activity of endothelin and the higher sensitivity of these animals to pulmonary hypertension (PH). (magiran.com)
  • Methods Using data from the PHAROS registry (a multicenter prospective observational study enrolling SSc patients with incident pulmonary hypertension), patients with group I PAH, 6 months of initial therapy with either an endothelin-receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE5), or a combination of ERA/PDE5 were included. (bmj.com)
  • Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. (druglib.com)
  • The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). (elsevier.com)
  • Using pooled pulmonary tissue from different regions of the lung, we performed a reverse-transcription polymerase chain reaction (RT-PCR) to determine ET B -receptor gene expression. (elsevier.com)
  • The ET B -receptor mRNA expression of the pooled pulmonary tissue showed a nonsignificant increase in affected horses compared with unaffected horses. (elsevier.com)
  • The airway hyperreactivity to ET-1 observed in the bronchial rings from the affected horses appears to be due in part to activation of pulmonary ET B receptors, which appear to be inactive in unaffected horses. (elsevier.com)
  • 2004. The endothelin system in pulmonary arterial hypertension. (koreascience.or.kr)
  • Abstract We previously showed that endothelin-1 expression was increased in vascular endothelium of deoxycorticosterone acetate-salt hypertensive rats, whereas in spontaneously hypertensive rats (SHR) it is similar to or less than that in normotensive rats. (ahajournals.org)
  • Abstract This study investigates the cellular localization and regulation of endothelin-1 (ET-1) and angiotensin II (Ang II) receptors and the effects of ET-1 and Ang II on [Ca 2+ ] i in cardiac hypertrophy due to volume overload in the rat. (ahajournals.org)
  • In contrast, the selective ETB-receptor agonist, IRL-1620 (1-1000 pmol) was found to be inactive. (lww.com)
  • Presence of contractile endothelin ETB receptors was studied by measuring the change in isometric tension in rings of left anterior descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ETB receptor agonist, Sarafotoxin 6c and endothelin-1. (lu.se)
  • Methods The migratory ability of peripheral neutrophils from healthy donors (HD) and different tumour cell lines (myeloid leukaemia HL60 cells and human pancreatic adenocarcinoma COLO357 cells) was analysed in response to N-Formylmethionyl-leucyl-phenylalanine (FMLP) or Protease-activated receptor 2 (Par-2) agonist. (bmj.com)
  • 481±25 μm in diameter) to cumulative concentrations (10 −10 to 10 −6 mol/L) of endothelin-1 (ET-1), and sarafotoxin 6c (S6c), a specific ETB-receptor agonist, were measured using a video dimension analyzer. (ahajournals.org)
  • The vascular effects of the endothelin B (ETB) receptor agonist IRL 1620 were investigated in the rat P22 carcinosarcoma and a range of normal tissues in BDIX rats. (whiterose.ac.uk)
  • The endothelin receptor antagonists inhibit the binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells which results in vasodilation. (nih.gov)
  • Endothelin-1 (ET-1) is a 21 amino acid peptide that acts in a paracrine and autocrine fashion as a potent vasoconstrictor. (nih.gov)
  • The endothelin (ET) system, like other vascular regulatory systems, consists of a parent peptide that undergoes enzymatic activation and exerts its biologic effects by modulating specific receptors. (ahajournals.org)
  • 1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and antinatriuretic effects of the endogenous vascular peptide endothelin. (portlandpress.com)
  • Orally active endothelin antagonists are now being developed, but little was known of endothelin's role as a renal peptide in humans. (portlandpress.com)
  • 3. Ligand binding, immunocytochemical, radioimmunoassay and molecular biological studies were used to establish endothelin as a renal peptide in man. (portlandpress.com)
  • Carrier-protein conjugated synthetic peptide encompassing a sequence within the N-terminus region of rat Endothelin B Receptor. (genetex.com)
  • Introduction: Endothelin-1 (ET-1) is a potent vasoactive peptide that acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (HS). (ovid.com)
  • ET A receptors are initially classfied according to the the rank order of potency of ET agonists with ET-1 being equipotent to ET-2 but ET-3 typically displaying 100 fold less potency and confirmed by using selective peptide antagonists (e.g. (guidetopharmacology.org)
  • Nous avons préalablement démontré que l'endothéline-1 (ET-1), un peptide vasoconstricteur de 21 acides aminés, joue un rôle central dans le métabolisme des tissus articulaires et a des fonctions cataboliques sur le cartilage articulaire dans l'ostéoarthrose, en liant son récepteur de type A (ETA). (umontreal.ca)
  • The author's laboratory has previously shown that endothelin-1 (ET-1), a 21-residue vasoconstrictive peptide, plays a central role in joint tissue metabolism, and has a catabolic function in matrix collagen degradation in osteoarthritis. (umontreal.ca)
  • Subtype-specific sorting of the ETA endothelin receptor by a novel endocytic recycling signal for G protein-coupled receptors. (springer.com)
  • Furthermore, S6c was a potent pressor agent in the pithed rat (ED25 mm Hg approximately 0.1 nmoles/kg, i.v.), suggesting that the ETB receptor subtype may be important in cardiovascular function. (nih.gov)
  • A subtype of endothelin receptor found predominantly in the KIDNEY. (curehunter.com)
  • A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. (curehunter.com)
  • Cloning of a cDNA encoding a non-isopeptide selective subtype of the endothelin receptor. (springer.com)
  • In conclusion, ET-1 receptor proportion is cell specific, with cardiomyocytes possessing predominantly the ET A subtype and fibroblasts possessing both ET A and ET B receptors. (ahajournals.org)
  • 16 19 20 Various cardiac effects, such as trophic effects, 21 collagen deposition in hypertrophied hearts, 22 and induction of ANP secretion, 20 are mediated via ET A subtype receptors. (ahajournals.org)
  • These effects occur primarily through ligation of the endothelin-1 receptor A subtype (ETA). (umontreal.ca)
  • This study demonstrates the presence of a novel endothelin (ET) receptor subtype that displays high affinity for both ET A - and ET B -selective ligands. (aspetjournals.org)
  • Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways. (springer.com)
  • The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene. (wikidoc.org)
  • Ceccherini I, Zhang A, Matera I, Yang G, Devoto M, Romeo G, Cass D (1995) Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat. (springer.com)
  • This may occur despite an augmented ET B -receptor mediated increase in vascular tone as seen in some peripheral arteries from obese animals, in particular in those of endothelin-1 gene overexpressing mice 1 and contribute to the less than expected vascular and metabolic phenotype. (nature.com)
  • Chromosomal assignments of the human endothelin family genes: The endothelin- 1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3. (springer.com)
  • Mutations of the receptor gene are responsible for Hirschsprung disease type 2, a multigenic disorder with phenotypes such as bicolored irides, megacolon, hypopigmentation, and hearing loss. (lsbio.com)
  • The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. (genetex.com)
  • Background- Peroxisome proliferator-activated receptor-α (PPAR-α) is a lipid-activated nuclear receptor that negatively regulates the vascular inflammatory gene response by interacting with transcription factors, nuclear factor-κB, and AP-1. (ahajournals.org)
  • 3 PPARs regulate gene expression by binding with retinoid X receptors as a heterodimeric partner to peroxisome proliferator response elements. (ahajournals.org)
  • 1,2 The effects of endothelin on vascular tone are mediated by two major types of endothelin receptors, A (ETA) and B (ETB), each encoded by a different gene. (ahajournals.org)
  • To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. (molvis.org)
  • ETB1 mediates vasodilation, When endothelin binds to ETB1 receptors, this leads to the release of nitric oxide (also called endothelium-derived relaxing factor), natriuresis and diuresis (the production and elimination of urine) and mechanisms that lower blood pressure. (wikipedia.org)
  • In human papillomavirus (HPV)-positive cervical cancer cells, the endothelin A receptor (ET A R) mediates an endothelin-1-induced mitogenic effect, thus representing a relevant target for antitumor therapy. (aacrjournals.org)
  • Endothelin mediates its biological activity in humans through the endothelin A and B receptors. (uzh.ch)
  • Until recently, it was thought that all cellular activities of the endothelins were mediated through their interactions with their cell surface receptors. (acris-antibodies.com)
  • Endothelins have also been implicated in a variety of pathophysiological conditions associated with stress including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure [ PMID: 18758495 ]. (ebi.ac.uk)
  • The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. (ebi.ac.uk)
  • However, in anesthetized rats, this compound markedly potentiated ET-1-induced renal vascular resistance, a response normally observed with selective ETB receptor antagonists. (biomedsearch.com)
  • Animal studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal damage. (portlandpress.com)
  • 4. The identification of species differences between man and rat directed further development of quantitative molecular biological methodology to permit analysis of endothelin receptors in human renal biopsies, and demonstrated perturbation of the system in the context of cyclosporin A therapy in renal transplantation. (portlandpress.com)
  • The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). (unboundmedicine.com)
  • Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals. (unboundmedicine.com)
  • No change in ETA receptor expression was observed in the renal medulla following HS, however, centhaquin produced decrease (-61%) in ETA levels compared to HS. (ovid.com)
  • HS decreased (-34%) ETB receptor expression in the renal medulla which was completely reversed by centhaquin and not saline. (ovid.com)
  • Conclusions: Centhaquin was found to be an effective resuscitative agent and induced an increase in ETB receptor expression in the renal medulla could lead to vasodilator effect and promote diuresis and natriuresis, preventing injury to the renal medulla. (ovid.com)
  • The NDA for our lead drug candidate Thelin(TM) (sitaxsentan sodium), an endothelin A receptor antagonist for the treatment of PAH, is now under active review by the Cardio- Renal Division of the FDA. (thefreedictionary.com)
  • Endothelin type B receptors (ETB-R) can induce vasodilation of the renal vasculature and also regulate tubular sodium handling. (physiology.org)
  • 18 report A Randomised, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Effect of the Endothelin Receptor Antagonist Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death in Patients With Type 2 Diabetes Mellitus and Diabetic Nephropathy (ASCEND) of patients with type 2 diabetes, proteinuria, and advanced CKD (mean eGFR approximately 30 ml/min). (asnjournals.org)
  • Pharmacology and physiopathology of the brain endothelin system: an overview. (ebi.ac.uk)
  • Goto K , Hama H , Kasuya Y . 1996 Molecular pharmacology and pathophysiological significance of endothelin. (springer.com)
  • Electrophysiological studies performed on Xenopus laevis oocytes injected with canine spleen poly(A) + RNA indicated that the ET B receptor present in these tissues is functional and displays the same pharmacology as that observed in binding studies using these membranes. (aspetjournals.org)
  • Although canine lung and cloned human ET B receptors displayed the same molecular weight bands with similar pharmacology, canine spleen ET B receptors displayed different molecular weight bands and different pharmacology. (aspetjournals.org)
  • ET exerts its effects through two types of endothelin receptors: type A (ETAR) and type B (ETBR). (springer.com)
  • ETAR and ETBR are G-protein-coupled receptors (GPCRs) that share homology with the rhodopsin family. (springer.com)
  • In humans, endothelins mediate their actions via two specific G-Protein coupled receptors, ETAR and ETBR. (acris-antibodies.com)
  • While ETAR has varying affinities for the endothelin isoforms (ET-1 >ET-2>ET-3), ETBR shows no selective affinity. (acris-antibodies.com)
  • Hypermethylation of the ETBR correlated with transcriptiol down-regulation and reduced expression of ETB receptor was observed in several prostate, bladder and colon cancer cell lines. (acris-antibodies.com)
  • GPR37L1 (G-protein coupled receptor 37-like 1), also called ETBR-LP-2 (endothelin B receptor-like. (biomol.com)
  • GPR37L1 (G-protein coupled receptor 37-like 1), also called ETBR-LP-2 (endothelin B receptor-like protein 2), is a 481aa, orphan 7-transmembrane receptor with calculated molecular weight of 53kD. (biomol.com)
  • In this study, a series of potent dipeptide sulfonamide dual-endothelin ETA/ETB receptor antagonists were prepared to investigate their potential benefit in vascular diseases. (biomedsearch.com)
  • Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. (biomedsearch.com)
  • It was found that CGS 31398 had potent affinity for the ETA receptor in rat and rabbit aorta with IC50 values of 0.87 and 0.79 nM, respectively. (biomedsearch.com)
  • Brown MA, Smith PL. Endothelin: a potent stimulator of intestinal ion secretion in vitro . (springer.com)
  • Endothelins are potent vasoconstrictors 1 endowed with hypertrophic and mitogenic potential. (ahajournals.org)
  • In conclusion, tezosentan, a potent mixed ET receptor antagonist with a short half-life, may offer a novel medical approach for the i.v. treatment of acute pathological conditions. (aspetjournals.org)
  • Endothelin-1 is a long-lasting potent vasoconstrictor and plays a key role in cardiovascular haemostasis. (uzh.ch)
  • Late cerebral ischaemia after subarachnoid haemorrhage: is cerebrovascular receptor upregulation the mechanism behind? (springer.com)
  • In pathological states, however, there could be upregulation of the ET B receptors located on smooth muscle cells that function similar to the ET A receptor, which amplify the vasoconstrictive and mitogenic effects of ET-1. (ahajournals.org)
  • Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensi. (biomedsearch.com)
  • The Role of MAPK Pathways in Airborne Fine Particulate Matter-Induced Upregulation of Endothelin Receptors in Rat Basilar Arteries. (genetex.com)
  • Nakano A , Kishi F , Minami K , Wakabayashi H , Nakaya Y , Kido H . 1997 Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acidlenght endothelins by chymase from human mastcells. (springer.com)
  • Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide. (ebi.ac.uk)
  • 22 The activation of ET B receptors stimulates the release of nitric oxide and prostacyclin and prevents apoptosis. (ahajournals.org)
  • In this study we investigate the contribution of both ET receptors as well as of the eicosanoids and nitric oxide to the vasoconstrictor properties of ET-1 in the guinea-pig kidney. (lww.com)
  • 1 Indeed, the inhibition of endogenous endothelium-derived relaxing factor (ie, nitric oxide) production in vivo results in an enhanced coronary microvessel vasoconstrictor response to ETB-receptor stimulation. (ahajournals.org)
  • Studies of these mechanical and vasogenic factors in the pathogenesis of glaucoma have turned attention to endothelin (ET) and nitric oxide (NO), two of the main cellular mediators involved in the regulation of IOP and local ocular blood flow. (molvis.org)
  • Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. (nature.com)
  • It is indicated that endothelin type A receptor (ETAR) plays a major role in ET1-mediated pathophysiological actions including diabetic pathology. (dovepress.com)
  • In another context, several studies have reported that endothelin-1 and its receptor ETAR also play a central role in the development of tumour cell invasion and metastasis. (bmj.com)
  • It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2. (curehunter.com)
  • The ETB receptor has similar affinity for all three endothelins and activates a phosphatidylinositol-calcium second messenger system. (lsbio.com)
  • 01), but AT 1 receptor affinity was unchanged after volume overload. (ahajournals.org)
  • The pA 2 values showed a nonsignificant decrease in ET A -receptor affinity and a significant increase in ET B -receptor affinity in affected horses compared with unaffected horses. (elsevier.com)
  • We therefore assessed the effect of Ambrisentan on metastatic carcinoma cell lines in response to protease-activated receptor 2 (PAR2) activation, which is a GPCR that has been implicated in tumor progression 22 , 23 , 24 . (nature.com)
  • Ambrisentan inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. (medscape.com)
  • We present the available published and presented data about ambrisentan, an ET(A)-selective endothelin receptor antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment of PAH in patients with WHO functional class II and III symptoms. (druglib.com)
  • Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis. (springer.com)
  • The intracellular signaling pathways and overall effects are somewhat different for the two receptors, and there may be an advantage to specific inhibition of the type A receptor as opposed to bimodal inhibition of both. (nih.gov)
  • 1996 Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. (springer.com)
  • In the current study, we focused on the ET-1-activated signal transduction pathways in cancer cells and found that ET-1, via activation of ETB receptors, induced expression of p53 and apoptotic cell death of A375 melanoma cells. (nii.ac.jp)
  • Targetting the endothelin system, potentially by modulating upstream pathways to prevent ETB receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life. (eur.nl)
  • Endothelin 1 signals via two distinctly different receptor-mediated pathways. (dissertations.se)
  • The following antibody was used in this experiment: Endothelin B Receptor Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-27173, RRID AB_2544649. (thermofisher.com)
  • Immunohistochemical staining of Adrenal (Medulla) using anti-Endothelin B Receptor antibody SP4124P. (acris-antibodies.com)
  • When conjugated with monomethyl auristatin E, the antibody-drug conjugate (ADC) showed remarkable efficacy against human melanoma cell lines and xenograft tumor models that was commensurate with levels of receptor expression. (aacrjournals.org)
  • This receptor is particularly attractive as a target for antibody-drug conjugate (ADC) therapy because of its minimal expression on normal tissue, its cell-surface localization, and rapid endocytosis. (aacrjournals.org)
  • Colocalization of ETB receptor immunostaining was performed using an antibody to neuritin, a selective marker of RGCs. (arvojournals.org)
  • Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. (springer.com)
  • Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. (lu.se)
  • We have previously shown that mRNA levels for ET-1, ET-3, and their receptors are upregulated under hyperhexosemic conditions. (diabetesjournals.org)
  • In this experiment lung ET-1 mRNA levels and lung mRNA expression for the ET(A) receptors were determined in lung tissue weekly (term = 42 days, intervals = 7 days). (magiran.com)
  • 2) ET_A receptor proteins were observed in the area posterior, the caudal solitary tract nucleus and dorsal nucleus of the vagus in rat brainstem, whereas ET_A mRNA was localized to only area posterior. (nii.ac.jp)
  • On the other hand, the distribution of ET_B receptor proteins was similar to that of ET_B mRNA, and the ET_B receptors were expressed in the glia cells. (nii.ac.jp)
  • Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. (springer.com)
  • Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis. (bmj.com)
  • BSCB disruption by traumatic SCI also generates harmful substances, including endothelins (ETs) ( 11 - 15 ), matrix metalloproteinases (MMPs) ( 7 , 9 , 10 ), inflammatory cytokines and reactive oxygen species (ROS) ( 3 - 6 , 8 ) that can induce programmed neuronal death and permanently impair neuron function. (spandidos-publications.com)
  • There was a threshold value of ETB receptor densities expressed by individual cells to induce these responses and the receptor densities were controlled by a cell-cycle-dependent manner. (nii.ac.jp)
  • When applied directly to the brain of rats in picomolar quantities as an experimental model of stroke, endothelin-1 caused severe metabolic stimulation and seizures with substantial decreases in blood flow to the same brain regions, both effects mediated by calcium channels. (wikipedia.org)
  • A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats. (wikipedia.org)
  • 1998 Endothelin-1 enhances thymocyte proliferation in monolaterally adrenalectomized rats with controlateral adrenocortical regeneration. (springer.com)
  • 6 Vascular responses to ET-1 7 and endothelin receptors and signaling 8 9 are reduced in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and we have speculated that the receptor downregulation found could result from enhanced vascular production of ET-1. (ahajournals.org)
  • The purpose of this study was to determine changes in ET A receptor expression in the retina in the Morrison's elevated IOP model of glaucoma in rats. (arvojournals.org)
  • This study was aimed at investigating whether there are any changes in the expression of ETB receptor in vivo in the Morrison's elevated intraocular pressure (IOP) model of glaucoma in rats. (arvojournals.org)
  • Andrzejewska A, Dlugosz JW, Augustynowicz A. Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats. (wjgnet.com)
  • In vivo prevention of ET-1-induced sudden death in 6 rats by pretreatment with endothelin receptor antagonist at a dose of 30 mg/kg p.o. (nih.gov)
  • Endothelins (ET-1, 2, and 3) are considered to be very powerful vasoconstrictive substances. (acris-antibodies.com)
  • Inhibitors of endothelin. (springer.com)
  • Patients received avosentan in a dosage of 25 or 50 mg/d on top of either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for a duration of 6 months. (asnjournals.org)
  • It is concluded that salicylates are allosteric inhibitors of ETA receptors. (aspetjournals.org)
  • A clinical comparison of an endothelin receptor antagonist and phosphodiesterase-5 inhibitors for treating digital ulcers of systemic sclerosis. (onmedica.com)
  • To assess the efficacy of an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitors (PDE5i) for treating systemic sclerosis (SSc)-related digital ulcers (DUs).This prospective, multicenter, observational cohort study recruited patients with active SSc-related DUs from 13 medical centers in South Korea. (onmedica.com)
  • Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C and phospholipase D, as well as cytosolic protein kinase activation. (ebi.ac.uk)
  • There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, which constricts the smooth muscles of the blood vessels, raising blood pressure, or relaxes the smooth muscles of the blood vessels, lowering blood pressure, among other functions. (wikipedia.org)
  • ET-1 exerts its major vascular effects through activation of 2 distinct G protein coupled ET A and ET B receptors. (ahajournals.org)
  • Belongs to the G-protein coupled receptor 1 family. (abcam.com)
  • Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. (wikidoc.org)
  • This Ile to Lys substitution at codon 118 is located within the first transmembrane domain of this seven-transmembrane domain Gprotein-coupled receptor protein. (springer.com)
  • The ETA receptor is a member of the endothelin receptor group of G-protein-coupled receptors that also includes ETB. (cellsciences.com)
  • Values are the number of amino acids in the predicted receptor protein. (aspetjournals.org)
  • The experiments indicate that organ culture of rat coronary arteries upregulate endothelin ETB receptor-mediated contraction by inducing synthesis of new protein. (lu.se)
  • Second, antibodies were raised to the receptor, conjugated with monomethyl auristatin E, and tested for efficacy against melanoma tumor models generated from cell lines. (aacrjournals.org)
  • Role of endothelin in cardiovascular disease. (ebi.ac.uk)
  • Since its discovery in 1988 1 , the role of endothelin in cardiovascular disease has been intensively studied. (ersjournals.com)
  • This study probably closes the discussion of the role of endothelin receptor antagonists in congestive heart failure: it is unfortunate to conclude that the endothelin receptor antagonists did not live up to their potential. (ersjournals.com)
  • Aim: We investigated the role of endothelin-1 (ET-1) in coronary microvascular spasm in a porcine model. (nii.ac.jp)
  • Importantly, this was well before albuminuria developed.The final part of this thesis was to investigate the role of endothelin signaling for the intrarenal hypoxia in a diabetic rat model. (dissertations.se)
  • Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. (springer.com)
  • Endothelin type B (ET B ) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk? (portlandpress.com)
  • Since its discovery in 1988, endothelin (ET) has been widely implicated in the pathophysiology of cardiovascular disease. (springer.com)
  • The endothelin system and its potential as a therapeutic target in cardiovascular disease. (springer.com)
  • RePub, Erasmus University Repository: Endothelin type B (ETB) receptors: Friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk? (eur.nl)
  • Therefore, the present study highlights the possibility that alterations in the localization of the ETB receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. (eur.nl)
  • The overall aims of this thesis were therefore to determine the temporal relationship between development of intrarenal hypoxia and kidney disease as well as elucidate the potential link between endothelin signaling, intrarenal hypoxia and kidney disease in experimental insulinopenic diabetes.It is well established that different mouse strains have different susceptibility for kidney and cardiovascular disease. (dissertations.se)
  • Results with ET receptor antagonists in congestive heart failure have been disappointing. (ahajournals.org)
  • Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. (hindawi.com)
  • The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis. (hindawi.com)
  • It may play a role in reducing systemic ENDOTHELIN levels. (curehunter.com)
  • Emerging evidence from animal studies and clinical trials indicates that systemic inhibition of endothelin1 (ET1) signaling by endothelin receptor antagonists improves pathological features of diabetes and its complications. (dovepress.com)
  • receptor antagonist is effective to prevent coronary microvascular spasm. (nii.ac.jp)
  • The aim of this study was to examine if endothelin ETB receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. (lu.se)
  • These studies were designed to test the hypothesis that experimental hypercholesterolemia is characterized by a differentially altered coronary contractile response to ETA- and ETB-receptor stimulation, in vitro. (ahajournals.org)
  • Thus, the ETB receptor has a role in regulation of coronary artery tone in both the steady-state and pathophysiological states. (ahajournals.org)
  • Both receptors are localised to non-vascular structures such as epithelial cells as well as occurring in the central nervous system (CNS) on glial cells and neurones, where they are thought to mediate neurotransmission and vascular functions [ PMID: 9239759 ]. (ebi.ac.uk)
  • ET receptor are also found in the nervous system where they may mediate neurotransmission and vascular functions. (wikipedia.org)
  • Simultaneous changes in intracellular calcium and tension induced by endothelin-1 and sarafotoxin S6. (biomedsearch.com)
  • Tezosentan competitively antagonizes the specific binding of 125 I-labeled ET-1 and of the selective ET B receptor ligands 125 I-labeled ET-3 and 125 I-labeled sarafotoxin S6c on cells and tissues carrying ET A and ET B receptors, with inhibitory constants in the nanomolar range, and has high water solubility. (aspetjournals.org)
  • ETB receptors can be selectively activated by Sarafotoxin 6c. (dissertations.se)
  • Endothelins stimulate the contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferens, stomach) and stimulate secretion in several tissues e.g., kidney, liver and adrenals [ PMID: 16340664 , PMID: 8480469 , PMID: 8466176 ]. (ebi.ac.uk)
  • Nussdorfer GG , Rossi GP , Malendowicz LK , Mazzocchi G . 1999 Autocrine-paracrine endothelin system in the physiology and pathology of steroid-secreting tissues. (springer.com)
  • Tissues were collected to analyze ETA and ETB receptor expression using Western blot technique. (ovid.com)
  • Subsequent studies have demonstrated the presence of endothelins in vascular as well as in non-vascular cells and tissues, having multiple biological activities. (acris-antibodies.com)
  • The Endothelin Receptor ETB is expressed in most tissues. (lsbio.com)
  • Peroxisome proliferator-activated receptor-α (PPAR-α) is abundant in tissues with high oxidative energy demands that depend on mitochondrial fatty acid oxidation as a primary energy source, such as the heart and liver. (ahajournals.org)
  • Recent studies performed on various tissues, including rat heart, have revealed the presence of ET-1 and its receptors in the heart. (ahajournals.org)
  • Thus, the data presented in this manuscript provide evidence for the presence of a novel ET B receptor in different tissues as well as different species including human. (aspetjournals.org)
  • selective ETB receptor antagonists (BQ-788 and A192621) which affect endothelin B receptors are used in research but have not yet reached the clinical trial stage. (wikipedia.org)
  • Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T: Cloning and functional expression of human cDNA for the ETB endothelin receptor. (drugbank.ca)
  • Cloning and expression of a cDNA encoding an endothelin receptor. (springer.com)
  • An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis - a pilot study. (genetex.com)
  • The receptor is available in the following formats: stable over-expression cell line, membrane preparation, or purified receptor in HEK293 or CHO. (cellsciences.com)
  • ETB receptor levels were unaltered following HS, however, centhaquin significantly increased (79%) ETB receptor expression in the abdominal aorta. (ovid.com)
  • Retinal sections were obtained from both the control and IOP-elevated eyes and analyzed for changes in ET A receptor expression using immunohistochemistry. (arvojournals.org)
  • Elevated intraocular pressure results in an increase in ET A receptor expression. (arvojournals.org)
  • Increased endothelin receptor expression is associated with neurodegeneration in glaucoma. (arvojournals.org)
  • The receptor was expressed on the vast majority of melanoma tissue specimens examined, and the ADC showed preclinical efficacy even in a model representing the low end of the expression range. (aacrjournals.org)
  • The receptors for endothelins were cloned shortly thereafter ( 4, 5 ) and their expression in various cell types, including melanocytes and melanoma cells, pointed to functions independent of their role in endothelium. (aacrjournals.org)
  • Retinas were sectioned and stained for ETB receptor expression by immunohistochemistry. (arvojournals.org)
  • Immunohistochemical analysis showed that IOP elevation caused increased expression of ETB receptor in the RGCs, inner plexiform layer (IPL) and inner nuclear layer (INL). (arvojournals.org)
  • Increased intraocular pressure caused increased ETB receptor expression possibly through pressure-related mechanism. (arvojournals.org)
  • The study showed that expression of endothelin in lungs of layers and broilers was similar during the first three weeks and the overall trend of ET-1 expression was increasing. (magiran.com)
  • The subsequent release of the nonapeptide vasodilator bradykinin (BK) in the joint microenvironment, and up-regulation of bradykinin receptor B1 (BKB1) expression, engenders a vicious cycle of synovial membrane inflammation, articular cartilage destruction, and joint pain. (umontreal.ca)
  • Expression levels of ETB receptors on the tumour vasculature could be useful for predicting which tumours are likely to respond to IRL 1620. (whiterose.ac.uk)
  • Concentrations of C-terminal pro-endothelin-1 (CT-proET1) in arterial blood were determined before and after infusion. (bmj.com)
  • Plasma and cardiac ET-1 concentrations and ET-1 receptor regulation on both ventricular cell types are not altered in cardiac volume overload, suggesting that cardiac ET-1 may not play a significant role in this model. (ahajournals.org)
  • Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. (molvis.org)
  • Polymorphic variants of endothelin EDN (K198N) and endothelin receptor type A genes EDN RA (C1222T, C70G, G231A) affected ET plasma concentrations. (molvis.org)
  • According to these results, plasma endothelin concentrations do not appear to be a marker for NTG. (molvis.org)
  • Serum samples were analysed for midkine concentrations as well as autoantibody titers against angiotensin II type 1 and endothelin-1 type A receptors. (minervamedica.it)
  • 1995. Circulating endothelin-1 concentrations in patients with chronic hypoxia. (koreascience.or.kr)
  • endothelin also has direct (toxic) myocardial effects 2 . (ersjournals.com)
  • Garvin J, Sanders K. Endothelin inhibits fluid and bicarbonate transport in part by reducing Na+/K+ ATPase activity in the rat proximal straight tubule. (springer.com)
  • The renin-angiotensin and endothelin systems are considered important pathophysiological effectors. (minervamedica.it)
  • The aim of this study was to assess whether circulating midkine serum levels in patients with peripheral artery disease correlate with established atherosclerosis risk factors, as well as titers of functional autoantibodies directed against receptors of the renin-angiotensin and endothelin system. (minervamedica.it)
  • Thus far, the therapeutic potential of endothelin receptor antagonists has seemed most promising. (ersjournals.com)
  • ET receptor antagonists therefore have a therapeutic potential in the acute treatment of emergency indications. (aspetjournals.org)
  • 1 first identified endothelin (ET), a novel polypeptide vasoconstrictor for which numerous other functions were identified later, 2 there was early widespread enthusiasm and great expectation for therapeutic opportunities. (asnjournals.org)
  • The results also suggest that: 1) irreversible ET-1 binding probably limits actions of receptor antagonists in vivo, and 2) an association of salicylates and ETA receptor antagonists should be used to evaluate the physiopathological role of ET-1 and may be of therapeutic interest in the treatment of ischemic heart disease. (aspetjournals.org)
  • These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. (ersjournals.com)
  • In mammals, the endothelin (ET) family comprises three endogenous isoforms, ET-1, ET-2 and ET-3. (guidetopharmacology.org)
  • ET-3 is unique in that it is the only endogenous isoform that distinguishes between the two endothelin receptors. (guidetopharmacology.org)
  • 1994. Contribution of endogenous generation of endothelin-1 to basal vascular tone. (koreascience.or.kr)
  • Endothelin, hypertension and chronic kidney disease: new insights. (springer.com)
  • Activation of the endothelin system has emerged as an important pathway in PE pathophysiology based on experimental PE models where endothelin receptor antagonists (ERAs) prevented or attenuated hypertension and proteinuria. (portlandpress.com)
  • Bakris noted that Gilead Sciences made a splash earlier this year when it released interim results showing dramatic additional blood pressure reductions with its selective endothelin A receptor antagonist darusentan in patients who had resistant hypertension despite maximal doses of a three-drug regimen that included a diuretic. (thefreedictionary.com)
  • Endothelin receptor dimers evaluated by FRET, ligand binding, and calcium mobilization. (springer.com)
  • The endothelin receptors differ in their ligand specificity. (acris-antibodies.com)
  • Therefore, A collaboration mechanism between the ET_A and the ET_B receptorS may function in the recognition of ET-1, a typical 'bivalent' ligand. (nii.ac.jp)
  • 6 We have reported that the production of ET-1 is markedly increased both in the hypertrophied heart and the failing heart 11-14 and that chronic treatment with ET type A receptor antagonists significantly inhibited the development of cardiac hypertrophy and heart failure. (ahajournals.org)
  • 2016) 'Endothelin' Pharmacol. (wikipedia.org)
  • Publications] Sakurai-Yamashita Y: 'Rat peritoneal macrophages express endothelin ET_B but not endothelin ET_A receptors' Eur.J.Pharmacol.338. (nii.ac.jp)
  • ET-1 receptor densities, affinities, and ET-1-induced [Ca 2+ ] i were not significantly different from control in both ventricular cell types from hypertrophied myocardium. (ahajournals.org)
  • Cardiac hypertrophy induced a significant downregulation of AT 1 receptors on fibroblasts, whereas total binding and [Ca 2+ ] i sensitivity to Ang II were significantly enhanced in hypertrophied cardiomyocytes. (ahajournals.org)
  • The results from blocking ETA and activating ETB receptors demonstrated that endothelin 1 signaling via ETA receptors contributes to intrarenal hypoxia in the rat diabetic kidney, and that ETB stimulation significantly reduces the diabetes-induced intrarenal hypoxia. (dissertations.se)