Endothelin receptor

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.

endothelin receptor type A
Identifiers
Symbol	EDNRA
NCBI gene	1909
HGNC	3179
OMIM	131243
RefSeq	NM_001957
UniProt	P25101
Other data
Locus	Chr. 4 q31.2
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endothelin receptor type B
Identifiers
Symbol	EDNRB
Alt. symbols	HSCR2, HSCR
NCBI gene	1910
HGNC	3180
OMIM	131244
RefSeq	NM_000115
UniProt	P24530
Other data
Locus	Chr. 13 q22
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Physiological functions

• ET_A is a subtype for vasoconstriction^[1] 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,^[1] 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^[1]
• ET_C has yet no clearly defined function.^[1]
• 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]

See also

• Endothelin receptor antagonist