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Endothelin

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Endothelin 1
Symbol(s): EDN1
Locus: 6 p23 -p24
EC number [5]
EntrezGene 1906
OMIM 131240
RefSeq NM_001955
UniProt P05305
Endothelin 2
Symbol(s): EDN2
Locus: 1 p34
EC number [6]
EntrezGene 1907
OMIM 131241
RefSeq NM_001956
UniProt P20800
Endothelin 3
Symbol(s): EDN3
Locus: 20 q13.2 -q13.3
EC number [7]
EntrezGene [8]
OMIM 131242
RefSeq NM_000114
UniProt P14138

Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. Among the strongest vasoconstrictors known, endothelins are implicated in vascular diseases of several organ systems, including the heart, general circulation and brain[1][2].

Isoforms

There are three isoforms with varying regions of expression and two key receptor types, ETA and ETB.

Brain and nerves

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[3]. A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats[4].

Balance

In a healthy individual, a delicate balance between vasoconstriction and vasodilation is maintained by endothelin, calcitonin 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.

References

  1. Agapitov AV, Haynes WG. Role of endothelin in cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2002 Mar;3(1):1-15.[1]
  2. Schinelli S. Pharmacology and physiopathology of the brain endothelin system: an overview. Curr Med Chem. 2006;13(6):627-38. [2]
  3. 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. [3]
  4. 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.[4]

External links


{{enWP|Endothelin]]

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