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There are at least four knownendothelin receptors, ET_A, ET_B1, ET_B2 and ET_C,^[1] all of which areG protein-coupled receptors whose activation result in elevation of intracellular-freecalcium,^[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

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ET_A is a subtype for vasoconstriction^[1] These receptors are found in thesmooth muscle tissue ofblood vessels, and binding ofendothelin to ET_A increases vasoconstriction (contraction of the blood vessel walls) and theretention ofsodium, leading to increasedblood pressure.^[3]
ET_B1 mediates vasodilation,^[1] When endothelin binds to ET_B1 receptors, this leads to the release ofnitric oxide (also calledendothelium-derived relaxing factor),natriuresis anddiuresis (the production and elimination of urine) and mechanisms that lower blood pressure.
ET_B2 mediates vasoconstriction^[1]
ET_C has yet no clearly defined function.^[1]
ET receptors are also found in the nervous system where they may mediateneurotransmission and vascular functions.^[4]

Brain and nerves

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Widely distributed in the body,receptors for endothelin are present in blood vessels and cells of the brain,choroid plexus and peripheralnerves. When applied directly to the brain of rats in picomolar quantities as an experimental model ofstroke, endothelin-1 caused severe metabolic stimulation andseizures with substantial decreases in blood flow to the same brain regions, both effects mediated bycalcium channels.^[5]

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

Clinical significance

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Mutations in the EDNRB gene are associated withABCD syndrome^[7] and some forms ofWaardenburg syndrome.^[8]

References

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^^a ^b ^c ^d ^eBoron WF, Boulpaep EL, eds. (2009).Medical physiology a cellular and molecular approach (2nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 480.ISBN 9781437720174.
^Davenport AP (2002). "International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature".Pharmacol. Rev.54 (2):219–26.CiteSeerX 10.1.1.546.8632.doi:10.1124/pr.54.2.219.PMID 12037137.S2CID 14264340.
^Hynynen MM, Khalil RA; Khalil (January 2006)."The vascular endothelin system in hypertension--recent patents and discoveries".Recent Pat Cardiovasc Drug Discov.1 (1):95–108.doi:10.2174/157489006775244263.PMC 1351106.PMID 17200683.
^Barnes K, Turner AJ; Turner (August 1997). "The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies".Neurochem. Res.22 (8):1033–40.doi:10.1023/A:1022435111928.PMID 9239759.S2CID 9101207.
^Gross PM, Zochodne DW, Wainman DS, Ho LT, Espinosa FJ, Weaver DF (July 1992). "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.doi:10.1016/0143-4179(92)90158-S.PMID 1331845.S2CID 24411443.
^Zochodne DW, Ho LT, Gross PM (December 1992). "Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve".Am. J. Physiol.263 (6 Pt 2): H1806–10.doi:10.1152/ajpheart.1992.263.6.H1806.PMID 1481904.
^Verheij JB, Kunze J, Osinga J, van Essen AJ, Hofstra RM (2002). "ABCD syndrome is caused by a homozygous mutation in the EDNRB gene".Am. J. Med. Genet.108 (3):223–5.doi:10.1002/ajmg.10172.PMID 11891690.
^Read AP, Newton VE (1997)."Waardenburg syndrome".J. Med. Genet.34 (8):656–65.doi:10.1136/jmg.34.8.656.PMC 1051028.PMID 9279758.

External links

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"Endothelin Receptors".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2012-02-04. Retrieved2006-07-21.
Endothelin+receptor at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

Cell surface receptor:G protein-coupled receptors

Class A:Rhodopsin-like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3
Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)
Serotonin	(all but5-HT3)5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)
Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 1 2 FPRL1 OXE Prostaglandin DP (1 2),EP (1 2 3 4),FP Prostacyclin Thromboxane
Other	Bile acid Cannabinoid (CB1 CB2,GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide

B/W (1
2)
FF (1
2)
S
Y (1
2
4
5)
Neuromedin (B
U (1
2))
Neurotensin (1
2)

Other

Anaphylatoxin (C3a
C5a (1
2))
Angiotensin (1
2)
Apelin
Bombesin
- BRS3
- GRPR
- NMBR)
- Bradykinin (B1
- B2)
Chemerin
- 1
- 2
Chemokine
Cholecystokinin (A
B)
Endothelin
- A
- B
Formyl peptide (1
2
3)
FSH
Galanin (1
2
3)
Gonadotropin-releasing hormone (1
2)
Ghrelin
Kisspeptin
Luteinizing hormone/choriogonadotropin
MAS (1
1L
D
E
F
G
X1
X2
X3
X4)
Melanocortin (1
2
3
4
5)
MCHR (1
2)
Motilin
Opioid (Delta
Kappa
Mu
Nociceptin &Zeta, but notSigma)
Orexin (1
2)
Oxytocin
Prokineticin (1
2)
Prolactin-releasing peptide
Relaxin (1
2
3
4)
Somatostatin (1
2
3
4
5)
Tachykinin (1
2
3)
Thyrotropin
Thyrotropin-releasing hormone
Urotensin-II
Vasopressin (1A
1B
2)

Miscellaneous

Taste, bitter	TAS2R 1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor type 1
Orphan	GPR (3 4 6 12 15 17 18 19 20 21 22 26 27 31 32 33 34 35 37 39 42 45 50 52 55 61 62 63 65 68 75 78 82 83 84 85 87 88 101 103 109A 119 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)
Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B:Secretin-like

Adhesion	ADGRB Brain-specific angiogenesis inhibitor 1 2 3 ADGRC Cadherin 1 2 3 ADGRE EMR 1 2 3 CD97 ADGRG 1 2 3 4 5 6 7 ADGRL Latrophilin 1 2 3 ELTD1
Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)
Other	Calcitonin CALCRL Corticotropin-releasing hormone (1 2) Glucagon (GR GIPR GLP1R GLP2R) Growth-hormone-releasing hormone PACAPR1 GPR Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C:Metabotropic glutamate /pheromone

Taste, sweet	TAS1R 1 2 3 Vomeronasal receptor, type 2
Other	Calcium-sensing receptor GABA_B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)