The alpha-2B adrenergic receptor (α_2B adrenoceptor), is a

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 ...

. It is a subtype of the adrenergic receptor 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 b ...

encoding this receptor has the symbol ADRA2B. ADRA2B

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

have been identified in several

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...

Receptor

α₂-adrenergic receptors include 3 highly homologous subtypes: α_2A, α_2B, and α_2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves 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 p ...

Clinical significance

This gene encodes the α_2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

. A polymorphic variant of the α_2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, 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-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced

basal metabolic rate Basal metabolic rate (BMR) is the rate of energy expenditure per unit time by 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 body mass J/(h·kg). Pro ...

obese Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no

introns An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...

in either its coding or

untranslated sequence A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non- ...

s. 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 of ...

, but was weakened in people without the variant. *

Evolution

The ''ADRA2B'' gene (sometimes referenced as ''A2AB'') is used in animals as a

nuclear DNA Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. I ...

phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of

, and contributed to reveal that

placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguishe ...

orders are distributed into four major clades:

Xenarthra Xenarthra (; from Ancient Greek ξένος, xénos, "foreign, alien" + ἄρθρον, árthron, "joint") is a major clade of placental mammals native to the Americas. There are 31 living species: the anteaters, tree sloths, and armadillos. ...

Afrotheria Afrotheria ( from Latin ''Afro-'' "of Africa" + ''theria'' "wild beast") is a clade of mammals, the living members of which belong to groups that are either currently living in Africa or of African origin: golden moles, elephant shrews (also k ...

Laurasiatheria Laurasiatheria ("laurasian beasts") is a superorder of placental mammals that groups together true insectivores ( eulipotyphlans), bats ( chiropterans), carnivorans, pangolins ( pholidotes), even-toed ungulates ( artiodactyls), odd-toed ungulat ...

, and

Euarchontoglires Euarchontoglires (synonymous with Supraprimates) is a clade and a superorder of mammals, the living members of which belong to one of the five following groups: rodents, lagomorphs, treeshrews, colugos, and primates. Evolutionary affinities wi ...

. 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 Imiloxan is a drug which is used in scientific research. It acts as a selective antagonist for the α2B adrenergic receptor, and has been useful for distinguishing the actions of the different α2 adrenergic subtypes. Synthesis The imidazole ...

Yohimbine Yohimbine (), also known as quebrachine, is an indole alkaloid derived from the bark of the African tree '' Pausinystalia johimbe''; also from the bark of the unrelated South American tree ''Aspidosperma quebracho-blanco''. Yohimbine is an α2 ...

Receptor

Clinical significance

Evolution

Research

Ligands

See also

References

External links

Further reading