The alpha-2B adrenergic receptor (α
2B adrenoceptor), is a
G-protein coupled receptor. It is a subtype of the
adrenergic receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
family. The human
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
encoding this receptor has the symbol ADRA2B.
ADRA2B
orthologs have been identified in several
mammals.
Receptor
α
2-adrenergic receptors include 3 highly homologous subtypes: α
2A, α
2B, and α
2C. These receptors have a critical role in regulating
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
release from
sympathetic nerves
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the ...
and from adrenergic neurons in the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
.
Clinical significance
This gene encodes the α
2B subtype, which was observed to associate with
eIF-2B
Eukaryotic Initiation Factor 2 (eIF2) is an eukaryotic initiation factor. It is required for most forms of eukaryotic Translation (biology), translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a Guanosine triphosphate, ...
, a
guanine nucleotide exchange protein
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
that functions in regulation of
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
. A polymorphic variant of the α
2B subtype, which lacks 3
glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
s from a glutamic acid
repeat element
Repeated sequences (also known as repetitive elements, repeating units or repeats) are short or long patterns of nucleic acids (DNA or RNA) that occur in multiple copies throughout the genome. In many organisms, a significant fraction of the genom ...
, was identified to have decreased
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 p ...
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
-mediated phosphorylation and
desensitization; this polymorphic form is also associated with reduced
basal metabolic rate
Basal metabolic rate (BMR) is the rate of food energy, energy expenditure per unit time by endotherm, endothermic animals at rest. It is reported in energy units per unit time ranging from watt (joule/second) to ml O2/min or joule per hour per kg b ...
in
obese subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no
introns in either its
coding or
untranslated sequences.
A deletion variant of the α
2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.
This variant also predisposed people who had it to focus more on negative aspects of a situation.
[
*] This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant
reboxetine
Reboxetine, sold under the brand name Edronax among others, is a drug of the norepinephrine reuptake inhibitor (NRI) class, marketed as an antidepressant by Pfizer for use in the treatment of major depression, although it has also been used off-l ...
, but was weakened in people without the variant.
[
*]
Evolution
The ''ADRA2B'' gene (sometimes referenced as ''A2AB'') is used in animals as a
nuclear DNA phylogenetic marker.
This intronless gene has first been used to explore the phylogeny of the major groups of
mammals,
and contributed to reveal that
placental orders are distributed into four major clades:
Xenarthra,
Afrotheria,
Laurasiatheria, and
Euarchontoglires. Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein–coupling. However, great variations are observed in the very long, third intracellular loop, with a polyglutamyl domain displaying pervasive length differences.
Research
A paper published on 28 June 2022 demonstrated that ADRA2B may be one of the potential targets of ALS. It is found that ADRA2B is upregulated in CNS transcriptomic fALS using an AI-enabled biological target discovery platform. With target discovery, several pathways and drugs can be further designed to treat ALS.
Ligands
; Agonists
* (−)-Dibromophakellin
; Antagonists
*
Imiloxan
*
Yohimbine
See also
*
Adrenergic receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
References
External links
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Further reading
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{{G protein-coupled receptors
Adrenergic receptors