Endothelin
2578537
221878681
2008-06-26T14:21:32Z
Paul144
1676299
/* Disease involvement */
{{protein | Name = [[Endothelin 1]] | caption = | image = | width = | HGNCid = 3176 | Symbol = [[EDN1]] | AltSymbols = | EntrezGene = 1906 | OMIM = 131240 | RefSeq = NM_001955 | UniProt = P05305 | PDB = | ECnumber = | Chromosome = 6 | Arm = p | Band = 23 | LocusSupplementaryData = -p24 }}
{{protein
| Name = Endothelin 2
| image =
| width =
| caption =
| Symbol = EDN2
| AltSymbols =
| ATC_prefix=
| ATC_suffix=
| ATC_supplemental=
| CAS_number=
| CAS_supplemental=
| DrugBank=
| EntrezGene = 1907
| HGNCid =3177
| OMIM = 131241
| PDB =
| RefSeq = NM_001956
| UniProt = P20800
| ECnumber =
| Chromosome = 1
| Arm = p
| Band = 34
| LocusSupplementaryData =
}}
{{protein
| Name = [[Endothelin 3]]
| image =
| width =
| caption =
| Symbol = [[EDN3]]
| AltSymbols =
| ATC_prefix=
| ATC_suffix=
| ATC_supplemental=
| CAS_number=
| CAS_supplemental=
| DrugBank=
| EntrezGene =
| HGNCid =3178
| OMIM = 131242
| PDB =
| RefSeq = NM_000114
| UniProt = P14138
| ECnumber =
| Chromosome = 20
| Arm = q
| Band = 13.2
| LocusSupplementaryData = -q13.3
}}
'''Endothelins''' are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure ([[hypertension]]) and heart disease.
Endothelins are 21-[[amino acid]] [[vasoconstriction|vasoconstricting]] [[peptide]]s produced primarily in the [[endothelium]] having a key role in [[smooth muscle|vascular homeostasis]]. Among the strongest vasoconstrictors known, endothelins are implicated in vascular diseases of several organ systems, including the heart, general circulation and brain<ref>Agapitov AV, Haynes WG. Role of endothelin in cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2002 Mar;3(1):1-15.[http://www.ncbi.nlm.nih.gov/pubmed/11984741]</ref><ref>Schinelli S. Pharmacology and physiopathology of the brain endothelin system: an overview. Curr Med Chem. 2006;13(6):627-38. [http://www.ncbi.nlm.nih.gov/pubmed/16529555]</ref>.
==Isoforms and organ distribution==
There are four [[isoform]]s (identified as ET-1, -2, -3, -4) with varying regions of expression and two key [[Receptor (biochemistry)|receptor]] types, [[Endothelin receptor|ET<sub>A</sub> and ET<sub>B</sub>]]<ref>[http://www.ncbi.nlm.nih.gov/pubmed/17200683 Hynynen MM, Khalil RA. The vascular endothelin system in hypertension--recent patents and discoveries. Recent Patents Cardiovasc Drug Discov. 2006 Jan;1(1):95-108.]</ref>.
* ET<sub>A</sub> receptors are found in the [[smooth muscle]] tissue of [[blood vessel]]s, and binding of endothelin to ET<sub>A</sub> increases vasoconstriction (contraction of the blood vessel walls) and the [[retention]] of [[sodium]], leading to increased [[blood pressure]].
* ET<sub>B</sub> is primarily located on the [[Endothelium|endothelial]] cells that line the interior of the blood vessels. When endothelin binds to ET<sub>B</sub> receptors, this leads to the release of [[nitric oxide]] (also called "NO" or [[endothelium-derived relaxing factor]]), [[natriuresis]] and [[diuresis]] (the production and elimination of urine) and mechanisms that lower blood pressure.
*Both types of ET receptor are found in the nervous system where they may mediate [[neurotransmission]] and vascular functions<ref>[http://www.ncbi.nlm.nih.gov/pubmed/9239759 Barnes K, Turner AJ. The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies. Neurochem Res. 1997 Aug;22(8):1033-40.]</ref>.
===Brain and nerves===
Widely distributed in the body, [[receptor]]s 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]]<ref>Gross PM, Zochodne DW, Wainman DS, Ho LT, Espinosa FJ, Weaver DF. Intraventricular endothelin-1 uncouples the blood flow: metabolism relationship in periventricular structures of the rat brain: involvement of L-type calcium channels. Neuropeptides. 1992 Jul;22(3):155-65. [http://www.ncbi.nlm.nih.gov/pubmed/1331845]</ref>. A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a [[peripheral neuropathy]] model in rats<ref>Zochodne DW, Ho LT, Gross PM. Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve. Am J Physiol. 1992 Dec;263(6 Pt 2):H1806-10.[http://www.ncbi.nlm.nih.gov/pubmed/1481904]</ref>.
==Examples of physiological interaction==
In a healthy individual, a delicate balance between vasoconstriction and [[vasodilation]] is maintained by endothelin and other vasoconstrictors on the one hand and nitric oxide, [[prostacyclin]] and other vasodilators on the other.
Overproduction of endothelin in the lungs may cause [[pulmonary hypertension]], which can sometimes be treated by the use of an [[endothelin receptor antagonist]], such as [[bosentan]] or [[sitaxsentan]]. The latter drug selectively blocks endothelin A receptors, decreasing the vasoconstrictive actions and allowing for increased beneficial effects of endothelin B stimulation, such as nitric oxide production. The precise effects of endothelin B receptor activation depends on the type of cells involved.
==Disease involvement==
The ubiquitous distribution of endothelin peptides and receptors implicates its involvement in a wide variety of physiological and pathological processes in the body. Among numerous diseases potentially occurring from endothelin dysregulation are
* several types of [[cancer]]<ref>[http://www.ncbi.nlm.nih.gov/pubmed/18325824 Bagnato A, Rosanò L. The endothelin axis in cancer. Int J Biochem Cell Biol. 2008;40(8):1443-51.]</ref>
* [[cerebral]] [[vasospasm]] following [[subarachnoid hemorrhage]]<ref>[http://www.ncbi.nlm.nih.gov/pubmed/17479073 Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nat Clin Pract Neurol. 2007 May;3(5):256-63.]</ref>
* [[arterial hypertension]] and other [[cardiovascular]] disorders<ref>[http://www.ncbi.nlm.nih.gov/pubmed/11984741 Agapitov AV, Haynes WG. Role of endothelin in cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2002 Mar;3(1):1-15.]</ref>
* [[pain]] mediation<ref>[http://www.ncbi.nlm.nih.gov/pubmed/15664691 Hasue F, Kuwaki T, Kisanuki YY, Yanagisawa M, Moriya H, Fukuda Y, Shimoyama M. Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice. Neuroscience. 2005;130(2):349-58.]</ref>
==References==
{{Reflist|2}}
==External links==
* [http://www.endothelinscience.com/ Endothelin science (Actelion Pharmaceuticals)]
* {{MeshName|Endothelins}}
[[Category:Peptides]]
[[Category:Hormones]]
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