endothelin receptor type A | |||||||
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Identifiers | |||||||
Symbol | EDNRA | ||||||
NCBI gene | 1909 | ||||||
HGNC | 3179 | ||||||
OMIM | 131243 | ||||||
RefSeq | NM_001957 | ||||||
UniProt | P25101 | ||||||
Other data | |||||||
Locus | Chr. 4 q31.2 | ||||||
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endothelin receptor type B | |||||||
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Identifiers | |||||||
Symbol | EDNRB | ||||||
Alt. symbols | HSCR2, HSCR | ||||||
NCBI gene | 1910 | ||||||
HGNC | 3180 | ||||||
OMIM | 131244 | ||||||
RefSeq | NM_000115 | ||||||
UniProt | P24530 | ||||||
Other data | |||||||
Locus | Chr. 13 q22 | ||||||
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There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, [1] all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, [2] 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.
Widely distributed in the body, receptors for endothelin are present in blood vessels and cells of the brain, choroid plexus and peripheral nerves. 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. [5]
A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats. [6]
Mutations in the EDNRB gene are associated with ABCD syndrome [7] and some forms of Waardenburg syndrome. [8]
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations. It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit muscle, the whole bundle or sheet of smooth muscle cells contracts as a syncytium.
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in controlling hemorrhage and reducing acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance. This makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.
In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.
Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.
Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases.
Albinism-black lock-cell migration disorder is the initialism for the following terms and concepts that describe a condition affecting a person's physical appearance and physiology: (1) A – albinism, (2) B – black lock of hair, (3) C – cell migration disorder of the neurocytes of the gut, and (4) D – sensorineural deafness. The syndrome is caused by mutation in the endothelin B receptor gene (EDNRB).
Vasomotor refers to actions upon a blood vessel which alter its diameter. More specifically, it can refer to vasodilator action and vasoconstrictor action.
Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of pulmonary hypertension. It is an endothelin receptor antagonist.
Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily.
Neuromedin U is a neuropeptide found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of blood pressure, pain perception, appetite, bone growth, and hormone release. It was first isolated from the spinal cord in 1985, and named after its ability to cause smooth muscle contraction in the uterus.
P2X purinoceptor 1, also ATP receptor, is a protein that in humans is encoded by the P2RX1 gene.
Endothelin receptor type B, (ET-B) is a protein that in humans is encoded by the EDNRB gene.
Endothelin receptor type A, also known as ETA, is a human G protein-coupled receptor.
Endothelin-3 is a protein that in humans is encoded by the EDN3 gene.
Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist (ERA) developed by Actelion and approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype. The drug received approval from the U.S. Food and Drug Administration (FDA) on October 13, 2013.
Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. Through oral administration, fimasartan blocks angiotensin II receptor type 1 (AT1 receptors), reducing pro-hypertensive actions of angiotensin II, such as systemic vasoconstriction and water retention by the kidneys. Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea on September 9, 2010, and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.
Sarafotoxins (SRTXs) are a group of toxins present in the venom of Atractaspis engaddensis, and in clinical trials cause similar symptoms to patients diagnosed with acute giardiasis. Their etymology is from the name of the snake "שרף עין גדי" in Hebrew, pronounced "Saraf Ein Gedi". Together with endothelins (ETs), they form a homogenous family of strong vasoconstrictor isopeptides. Among them, a few slightly different substances can be named as SRTX-a, SRTX-b, SRTX-c, which were initially derived from A. engaddensis. Each one contains twenty-one amino acid residues that spontaneously fold into a defined tertiary structure, with two interchain-cysteine linkages and a long hydrophobic tail. There are also other compounds, however, they are mostly derivations of previously mentioned ones. The main differences in the family of endothelin and sarafotoxins appear at N-terminal of peptides, as C-terminal in all of them is almost the same.
Waardenburg syndrome type 4A is an extremely rare congenital disorder caused by a mutation in an endothelin receptor gene. It results in common Waardenburg syndrome symptoms such as abnormal hair and skin pigmentation and heterochromia, but also present with symptoms of Hirschsprung's disease. Symptoms include abdominal pain and bowel obstruction. Waardenburg syndrome type 4A is the rarest among the types, appearing only once in about every 1,000,000 individuals. There have only been a total of 50 cases reported in total as of 2016.