Endothelin receptor

endothelin receptor type A

Identifiers
Symbol| EDNRA
Entrez| 1909
HUGO| 3179
OMIM| 131243
RefSeq| NM_001957
UniProt| P25101
Other data
Locus| Chr. 4 q31.2
endothelin receptor type B

Identifiers
Symbol| EDNRB
Alt. symbols| HSCR2, HSCR
Entrez| 1910
HUGO| 3180
OMIM| 131244
RefSeq| NM_000115
UniProt| P24530
Other data
Locus| Chr. 13 q22

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.

## Contents

* 1 Physiological functions
* 1.1 Brain and nerves
* 2 Clinical significance
* 3 See also
* 4 References
* 5 Further reading
* 6 External links

## Physiological functions

[edit | edit source]

* ETA is a subtype for vasoconstriction[1] These receptors are found in the smooth muscle tissue of blood vessels, and binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure.[3]
* ETB1 mediates vasodilation,[1] When endothelin binds to ETB1 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.
* ETB2 mediates vasoconstriction[1]
* ETC has yet no clearly defined function.[1]
* ET receptor are also found in the nervous system where they may mediate neurotransmission and vascular functions.[4]

### Brain and nerves

[edit | edit source]

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

[edit | edit source]

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

## See also

[edit | edit source]

* Endothelin receptor antagonist

## References

[edit | edit source]

1. ↑ 1.0 1.1 1.2 1.3 1.4 Walter F. Boron, Emile L. Boulpaep, eds. (2009). Medical physiology a cellular and molecular approach (2nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 480\. ISBN 9781437720174.
2. ↑ 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.
3. ↑ 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.
4. ↑ 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.
5. ↑ 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.
6. ↑ 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.
7. ↑ 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.
8. ↑ 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.

## Further reading

[edit | edit source]

* Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ. (2016) 'Endothelin' Pharmacol. Rev. 68: 357-418. pmid =26956245 doi =10.1124/pr.115.011833

## External links

[edit | edit source]

* "Endothelin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
* Endothelin+receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

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 but 5-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)
* Angiotensin (1
* 2)
* Apelin
* Bombesin
* BRS3
* GRPR
* NMBR)
* Bradykinin (B1
* B2)
* 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 not Sigma)
* 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|

| Orphan|

* GPR (1
* 3
* 4
* 6
* 12
* 15
* 17
* 18
* 19
* 20
* 21
* 22
* 23
* 25
* 26
* 27
* 31
* 32
* 33
* 34
* 35
* 37
* 39
* 42
* 44
* 45
* 50
* 52
* 55
* 61
* 62
* 63
* 65
* 68
* 75
* 77
* 78
* 81
* 82
* 83
* 84
* 85
* 87
* 88
* 92
* 101
* 103
* 109A
* 109B
* 119
* 120
* 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|

* ADGRG (1
* 2
* 3
* 4
* 5
* 6
* 7)

|

Orphan|

* GPR (56
* 64
* 97
* 98
* 110
* 111
* 112
* 113
* 114
* 115
* 116
* 123
* 124
* 125
* 126
* 128
* 133
* 143
* 144
* 155
* 157)

Other|

* Brain-specific angiogenesis inhibitor (1
* 2
* 3)
* Cadherin (1
* 2
* 3)
* Calcitonin
* CALCRL
* CD97
* Corticotropin-releasing hormone (1
* 2)
* EMR (1
* 2
* 3)
* Glucagon (GR
* GIPR
* GLP1R
* GLP2R)
* Growth-hormone-releasing hormone
* PACAPR1
* GPR
* Latrophilin (1
* 2
* 3
* ELTD1)
* Methuselah-like proteins
* Parathyroid hormone (1
* 2)
* Secretin
* Vasoactive intestinal peptide (1
* 2)

Class C: Metabotropic glutamate / pheromone

| Taste|

* TAS1R (1
* 2
* 3)
* 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)

|

Other|

* Calcium-sensing receptor
* GABAB (1
* 2)
* Glutamate receptor (Metabotropic glutamate (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8))
* GPRC6A
* GPR (156
* 158
* 179)
* RAIG (1
* 2
* 3
* 4)

Class F: Frizzled & Smoothened

| Frizzled|

* Frizzled (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10)

|

Smoothened|

* Smoothened

* v
* t
* e

Signaling peptide/protein receptor modulators

Adiponectin|

| AdipoR1|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* (–)-Arctigenin
* Arctiin
* Gramine
* Matairesinol

* Antagonists: Peptide: ADP-400

|

AdipoR2|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* Deoxyschizandrin
* Parthenolide
* Syringing
* Taxifoliol

* Antagonists: Peptide: ADP-400

Angiotensin|

* See here instead.

Bradykinin|

* Agonists: Bradykinin
* Kallidin

* Antagonists: FR-173657
* Icatibant
* LF22-0542

CGRP|

* Agonists: Amylin
* CGRP
* Pramlintide

* Antagonists: Atogepant
* BI 44370 TA
* CGRP (8-37)
* MK-3207
* Olcegepant
* Rimegepant
* SB-268262
* Telcagepant
* Ubrogepant

* Antibodies: Eptinezumab
* Erenumab
* Fremanezumab
* Galcanezumab

Cholecystokinin|

| CCKA|

* Agonists: Cholecystokinin

* Antagonists: Amiglumide
* Asperlicin
* Devazepide
* Dexloxiglumide
* Lintitript
* Lorglumide
* Loxiglumide
* Pranazepide
* Proglumide
* Tarazepide
* Tomoglumide

|

CCKB|

* Agonists: Cholecystokinin
* CCK-4
* Gastrin
* Pentagastrin (CCK-5)

* Antagonists: Ceclazepide
* CI-988 (PD-134308)
* Itriglumide
* L-365,360
* Netazepide
* Proglumide
* Spiroglumide

Unsorted|

* Antagonists: Nastorazepide

CRH|

| CRF1|

* Agonists: Cortagine
* Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Stressin I
* Urocortin

* Antagonists: Antalarmin
* Astressin-B
* CP-154,526
* Emicerfont
* Hypericin
* LWH-234
* NBI-27914
* NBI-74788
* Pexacerfont
* R-121919
* TS-041
* Verucerfont

|

CRF2|

* Agonists: Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Urocortin

* Antagonists: Astressin-B

Cytokine|

See here instead.

Endothelin|

* Agonists: Endothelin 1
* Endothelin 2
* Endothelin 3
* IRL-1620

* Antagonists: A-192621
* ACT-132577
* Ambrisentan
* Aprocitentan
* Atrasentan
* Avosentan
* Bosentan
* BQ-123
* BQ-788
* Clazosentan
* Darusentan
* Edonentan
* Enrasentan
* Fandosentan
* Feloprentan
* Macitentan
* Nebentan
* Sitaxentan
* Sparsentan
* Tezosentan
* Zibotentan

Galanin|

| GAL1|

* Agonists: Galanin
* Galanin (1-15)
* Galanin-like peptide
* Galmic
* Galnon
* NAX 810-2

* Antagonists: C7
* Dithiepine-1,1,4,4-tetroxide
* Galantide (M15)
* M32
* M35
* M40
* SCH-202596

|

GAL2|

* Agonists: Galanin
* Galanin (1-15)
* Galanin (2-11)
* Galanin-like peptide
* Galmic
* Galnon
* J18
* NAX 810-2

* Antagonists: C7
* Galantide (M15)
* M32
* M35
* M40
* M871

GAL3|

* Agonists: Galanin
* Galanin (1-15)
* Galmic
* Galnon

* Antagonists: C7
* Galantide (M15)
* GalR3ant
* HT-2157
* M32
* M35
* M40
* SNAP-37889
* SNAP-398299

Ghrelin/GHS|

* See here instead.

GH|

* See here instead.

GHRH|

* See here instead.

GLP|

| GLP-1|

* Agonists: Albiglutide
* Beinaglutide
* Dulaglutide
* Efpeglenatide
* Exenatide
* GLP-1
* Langlenatide
* Liraglutide
* Lixisenatide
* Oxyntomodulin
* Pegapamodutide
* Semaglutide
* Taspoglutide

|

GLP-2|

* Agonists: Apraglutide
* Elsiglutide
* Glepaglutide
* GLP-2
* Teduglutide

Others|

* Propeptides: Preproglucagon
* Proglucagon

Glucagon|

* Agonists: Dasiglucagon
* Glucagon
* Oxyntomodulin

* Antagonists: Adomeglivant
* L-168,049
* LGD-6972

* Propeptides: Preproglucagon
* Proglucagon

GnRH|

* See here instead.

Gonadotropin|

* See here instead.

Growth factor|

See here instead.

Insulin|

* Agonists: Chaetochromin (4548-G05)
* Insulin-like growth factor 1
* Insulin-like growth factor 2
* Insulin
* Insulin aspart
* Insulin degludec
* Insulin detemir
* Insulin glargine
* Insulin glulisine
* Insulin lispro
* Mecasermin
* Mecasermin rinfabate

* Antagonists: BMS-754807
* S661
* S961

* Kinase inhibitors: Linsitinib

* Antibodies: Xentuzumab (against IGF-1 and IGF-2)

Kisspeptin|

* Agonists: Kisspeptin
* Kisspeptin-10

* Antagonists: Kisspeptin-234

Leptin|

* Agonists: Leptin
* Metreleptin

MCH|

| MCH1|

* Agonists: Melanin concentrating hormone

* Antagonists: ATC-0065
* ATC-0175
* GW-803430
* NGD-4715
* SNAP-7941
* SNAP-94847

|

MCH2|

* Agonists: Melanin concentrating hormone

Melanocortin|

* See here instead.

Neuropeptide FF|

* Agonists: Neuropeptide AF
* Neuropeptide FF
* Neuropeptide SF (RFRP-1)
* Neuropeptide VF (RFRP-3)

* Antagonists: BIBP-3226
* RF9

Neuropeptide S|

* Agonists: Neuropeptide S

* Antagonists: ML-154
* SHA-68

Neuropeptide Y|

| Y1|

* Agonists: Neuropeptide Y
* Peptide YY

* Antagonists: BIBO-3304
* BIBP-3226
* BVD-10
* GR-231118
* PD-160170

|

Y2|

* Agonists: 2-Thiouridine 5'-triphosphate
* Neuropeptide Y
* Neuropeptide Y (13-36)
* Peptide YY
* Peptide YY (3-36)

* Antagonists: BIIE-0246
* JNJ-5207787
* SF-11

Y4|

* Agonists: GR-231118
* Neuropeptide Y
* Pancreatic polypeptide
* Peptide YY

* Antagonists: UR-AK49

Y5|

* Agonists: BWX-46
* Neuropeptide Y
* Peptide YY

* Antagonists: CGP-71683
* FMS-586
* L-152,804
* Lu AA-33810
* MK-0557
* NTNCB
* Velneperit (S-2367)

Neurotensin|

| NTS1|

* Agonists: Neurotensin
* Neuromedin N

* Antagonists: Meclinertant
* SR-142948

|

NTS2|

* Agonists: Neurotensin

* Antagonists: Levocabastine
* SR-142948

Opioid|

See here instead.

Orexin|

| OX1|

* Agonists: Orexin (A, B)

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* Filorexant
* Lemborexant
* Nemorexant
* RTIOX-276
* SB-334867
* SB-408124
* SB-649868
* Suvorexant
* TCS-1102

|

OX2|

* Agonists: Orexin (A, B)
* SB-668875

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* EMPA
* Filorexant
* JNJ-10397049
* Lemborexant
* MK-1064
* SB-649868
* Seltorexant
* Suvorexant
* TCS-1102
* TCS-OX2-29

Oxytocin|

* See here instead.

Prolactin|

* Agonists: Growth hormone
* Human placental lactogen
* Placental growth hormone (growth hormone variant)
* Prolactin
* S179D-hPRL
* Somatotropin

* Antagonists: Δ1–9-G129R-hPRL
* Δ1–14-G129R-hPRL
* G120K-hGH
* G129R-hPRL

* Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, metoclopramide, risperidone)
* Estrogens (e.g., estradiol)
* Progestogens (e.g., progesterone)

PTH|

* Agonists: Abaloparatide
* Parathyroid hormone
* Parathyroid hormone-related protein (PTHrP)
* Semparatide
* Teriparatide

Relaxin|

* Agonists: Insulin-like factor 3
* Relaxin (1, 2, 3)
* Serelaxin

Somatostatin|

* See here instead.

Tachykinin|

* See here instead.

TRH|

* Agonists: Azetirelin
* Fertirelin
* Montirelin
* Orotirelin
* Posatirelin
* Protirelin
* Rovatirelin
* Taltirelin
* TRH (TRF)

TSH|

* Agonists: Thyrotropin alfa
* TSH (thyrotropin)

Vasopressin|

* See here instead.

VIP/PACAP|

| VIPR1|

* Agonists: Peptide: Bay 55-9837
* LBT-3393
* PACAP
* VIP

|

VIPR2|

* Agonists: Peptide: LBT-3627
* PACAP
* VIP

PAC1|

* Agonists: PACAP
* PACAP (1-27)
* PACAP (1-38)

* Antagonists: PACAP (6-38)

Unsorted|

* PHI
* PHM
* PHV

Others|

* Endogenous: Adrenomedullin
* Apelin
* Asprosin
* Bombesin
* Calcitonin
* Carnosine
* CART
* CLIP
* DSIP
* Enteroglucagon
* Formyl peptide
* GALP
* GIP
* GRP
* Integrin ligands (collagens, fibrinogen, fibronectin, laminins, ICAM-1, ICAM-2, osteopontin, VCAM-1, vitronectin)
* Kininogens
* Motilin
* Natriuretic peptides (ANP, BNP, CNP, urodilatin)
* Nesfatin-1
* Neuromedin B
* Neuromedin N
* Neuromedin S
* Neuromedin U
* Obestatin
* Osteocalcin
* Resistin
* Secretin
* Thymopoietin
* Thymosins
* Thymulin
* Urotensin-II
* VGF

* Exogenous: Lifitegrast (LFA-1 antagonist)

See also
Receptor/signaling modulators

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