Endothelin receptor

Physiological functions

• ETA is a subtype for vasoconstriction 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.
• ETB1 mediates vasodilation, 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
• ETC has yet no clearly defined function.
• ET receptors are also found in the nervous system where they may mediate neurotransmission and vascular functions.

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.

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

Clinical significance

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

References

References

1. (2009). "Medical physiology a cellular and molecular approach". Saunders/Elsevier.
2. Davenport AP. (2002). "International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature". Pharmacol. Rev..
3. Hynynen MM, Khalil RA. (January 2006). "The vascular endothelin system in hypertension--recent patents and discoveries". Recent Pat Cardiovasc Drug Discov.
4. Barnes K, Turner AJ. (August 1997). "The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies". Neurochem. Res..
5. (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.
6. (December 1992). "Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve". Am. J. Physiol..
7. (2002). "ABCD syndrome is caused by a homozygous mutation in the EDNRB gene". Am. J. Med. Genet..
8. (1997). "Waardenburg syndrome". J. Med. Genet..