Endothelin receptor explained

There are at least four known endothelin receptors, ET_A, ET_B1, ET_B2 and ET_C,^[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.

Physiological functions

ET_A is a subtype for vasoconstriction These receptors are found in the smooth muscle tissue of blood vessels, and binding of endothelin to ET_A increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure.^[3]
ET_B1 mediates vasodilation, When endothelin binds to ET_B1 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.
ET_B2 mediates vasoconstriction
ET_C has yet no clearly defined function.
ET receptors are also found in the nervous system where they may mediate neurotransmission and vascular functions.^[4]

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.^[5]

A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats.^[6]

Clinical significance

Mutations in the EDNRB gene are associated with ABCD syndrome^[7] and some forms of Waardenburg syndrome.^[8]

External links

Web site: Endothelin Receptors . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2006-07-21 . 2012-02-04 . https://web.archive.org/web/20120204065748/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1283 . dead .

Notes and References

Book: ((Walter F. Boron)), ((Emile L. Boulpaep)). Medical physiology a cellular and molecular approach. 2009. Saunders/Elsevier. Philadelphia, PA. 9781437720174. 480. 2nd.
Davenport AP . International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature . Pharmacol. Rev. . 54 . 2 . 219–26 . 2002 . 12037137 . 10.1124/pr.54.2.219 . 10.1.1.546.8632 . 14264340 .
Hynynen MM, Khalil RA . The vascular endothelin system in hypertension--recent patents and discoveries . Recent Pat Cardiovasc Drug Discov . 1 . 1 . 95–108 . January 2006 . 17200683 . 1351106 . 10.2174/157489006775244263. Khalil .
Barnes K, Turner AJ . The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies . Neurochem. Res. . 22 . 8 . 1033–40 . August 1997 . 9239759 . 10.1023/A:1022435111928. Turner . 9101207 .
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 . 22 . 3 . 155–65 . July 1992 . 1331845 . 10.1016/0143-4179(92)90158-S. 24411443 .
Zochodne DW, Ho LT, Gross PM . Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve . Am. J. Physiol. . 263 . 6 Pt 2 . H1806–10 . December 1992 . 1481904 . 10.1152/ajpheart.1992.263.6.H1806.
Verheij JB, Kunze J, Osinga J, van Essen AJ, Hofstra RM . ABCD syndrome is caused by a homozygous mutation in the EDNRB gene . Am. J. Med. Genet. . 108 . 3 . 223–5 . 2002 . 11891690 . 10.1002/ajmg.10172.
Read AP, Newton VE . Waardenburg syndrome . J. Med. Genet. . 34 . 8 . 656–65 . 1997 . 9279758 . 10.1136/jmg.34.8.656. 1051028 .