There are at least four known
endothelin
Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute ...
receptors, ET
A, ET
B1, ET
B2 and ET
C,
all of which are
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...
s whose activation result in elevation of intracellular-free
calcium
Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
,
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
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
tissue of
blood vessel
Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s, and binding of
endothelin
Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute ...
to ET
A increases vasoconstriction (contraction of the blood vessel walls) and the
retention of
sodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
, leading to increased
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
.
*ET
B1 mediates vasodilation,
When endothelin binds to ET
B1 receptors, this leads to the release of
nitric oxide
Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
(also called
endothelium-derived relaxing factor
The Endothelium-derived relaxing factor (EDRF) is a strong Vasodilation, vasodilator produced by Endothelial cells, cardiac endothelial cells in response to stress signals such as high levels of ADP-ribosylation, ADP accumulation or Hypoxia (medic ...
),
natriuresis
Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by Brain natriuretic peptide, ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldost ...
and
diuresis
Diuresis () is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance.
In healthy people, ...
(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
Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...
and vascular functions.
Brain and nerves
Widely distributed in the body,
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
s for endothelin are present in blood vessels and cells of the brain,
choroid plexus
The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central ...
and peripheral
nerves
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...
. When applied directly to the brain of rats in picomolar quantities as an experimental model of
stroke
Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, endothelin-1 caused severe metabolic stimulation and
seizures
A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
with substantial decreases in blood flow to the same brain regions, both effects mediated by
calcium channels
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...
.
A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a
peripheral neuropathy
Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
model in rats.
Clinical significance
Mutations in the EDNRB gene are associated with
ABCD syndrome and some forms of
Waardenburg syndrome
Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...
.
See also
*
Endothelin receptor antagonist
An endothelin receptor antagonist (ERA) is a drug that blocks endothelin receptors.
Three main kinds of ERAs exist:
* Dual ET Receptor Antagonists, which affect both endothelin A (ETA) and B receptors (ETB)CPU0213 21780-32-9is an example of a ...
References
Further reading
* 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
*
*
G protein-coupled receptors
{{transmembranereceptor-stub