Beta-2 adrenergic receptor
Encyclopedia
The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene
encoding it.
less. Different polymorphic forms, point mutation
s, and/or downregulation of this gene are associated with nocturnal asthma
, obesity
and type 2 diabetes.
CaV1.2. This receptor-channel complex is coupled
to the Gs
G protein
, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate
(cAMP) which then activates protein kinase A, and the counterbalancing phosphatase
PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.
Beta-2 Adrenergic Receptors have also been found to couple with Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 Adrenergic Receptors are coupled only to Gs, and stimulation of these results in a more diffuse cellular response. This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.
increases intraocular pressure via net:
In glaucoma
, drainage is reduced ( open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol
may be employed.
s)
* denotes selective agonists to the receptor.
with Delta Opioid receptor
, Sodium-hydrogen antiporter 3 regulator 1
, AKAP12
and Grb2
.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
encoding it.
Gene
The gene is intronIntron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
less. Different polymorphic forms, point mutation
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
s, and/or downregulation of this gene are associated with nocturnal asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and type 2 diabetes.
Structure
The 3D crystallographic structure (see figure to the right) of the β2-adrenergic receptor has been determined .Mechanism
This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channelL-type calcium channel
The L-type calcium channel is a type of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. Like the others of this class, the α1 subunit is the one that determines most of the channel's properties....
CaV1.2. This receptor-channel complex is coupled
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
to the Gs
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...
G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
(cAMP) which then activates protein kinase A, and the counterbalancing phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.
Beta-2 Adrenergic Receptors have also been found to couple with Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 Adrenergic Receptors are coupled only to Gs, and stimulation of these results in a more diffuse cellular response. This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.
Muscular system
Tissue/Effect | Function | |
---|---|---|
Smooth muscle Smooth muscle Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by... relaxation in: |
uterus Uterus The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species... |
|
GI tract (decreases motility) | Delay digestion Digestion Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones.... during fight-or-flight response Fight-or-flight response The fight-or-flight response was first described by Walter Bradford Cannon.... |
|
detrusor urinae muscle of bladder Urinary bladder The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor... wall This effect is stronger than the alpha-1 receptor effect of contraction. |
Delay need of micturition | |
seminal tract Seminal tract The seminal tract is a part of the male reproductive system and consists of Seminiferous tubules , Epididymis , Vas deferens and Ejaculatory duct.... |
||
bronchi | Facilitate respiration Respiration (physiology) 'In physiology, respiration is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction... (agonists can be useful in treating asthma Asthma Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath... ) |
|
|
Increase perfusion of organs | needed during fight-or-flight |
striated muscle Striated muscle Striated muscle tissue is a form of fibers that are combined into parallel fibers. More specifically, it can refer to:* Cardiac muscle .* Skeletal muscle* Branchiomeric muscles... |
Tremor (via PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release) | |
Increased mass and contraction speed | fight-or-flight | |
glycogenolysis Glycogenolysis Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate... |
provide glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... fuel |
|
Circulatory system
- Increase cardiac outputCardiac outputCardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
(minor degree compared to β1).- Increase heart rateHeart rateHeart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
in sinoatrial nodeSinoatrial nodeThe sinoatrial node is the impulse-generating tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. It is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava...
(SA node) (chronotropicChronotropicChronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...
effect). - Increase atrial cardiac muscleCardiac muscleCardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
contractility. (inotropic effect). - Increases contractility and automaticity of ventricular cardiac muscle.
- Increase heart rate
- Dilate hepatic arteryHepatic arteryHepatic artery can refer to:* Common hepatic artery * Hepatic artery proper...
. - Dilate arteries to skeletal muscleSkeletal muscleSkeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
.
Eye
In the normal eye, beta-2 stimulation by salbutamolSalbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
increases intraocular pressure via net:
- Increase in production of aqueous humourAqueous humourThe aqueous humour is a clear, gelatinous fluid similar to plasma, but containing low-protein concentrations. It is secreted from the ciliary epithelium, a structure supporting the lens. It is located in the space between the lens and the cornea...
by the ciliary process, - Subsequent increased pressure-dependent uveoscleral outflow of humour, despite reduced drainage of humour via the Canal of Schlemm.
In glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, drainage is reduced ( open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol
Timolol
Timolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches...
may be employed.
Digestive system
- GlycogenolysisGlycogenolysisGlycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...
and gluconeogenesisGluconeogenesisGluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
in liver. - GlycogenolysisGlycogenolysisGlycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...
and lactateLactic acidLactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
release in skeletal muscleSkeletal muscleSkeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
. - Contract sphincters of GI tract.
- InsulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
secretion from pancreasPancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. - Thickened secretions from salivary glandSalivary glandThe salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
s.
Other
- Inhibit histamineHistamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
-release from mast cells. - Increase protein content of secretions from lacrimal glandLacrimal glandThe lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called...
s. - Increase reninReninRenin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
secretion from kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
. - Receptor also present in cerebellumCerebellumThe cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
. - Bronchiole dilation (targeted while treating asthma attacks)
- Involved in brain - immune - communication
Agonists
- spasmolyticMuscle relaxantA muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
s in asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
and COPDChronic obstructive pulmonary diseaseChronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
- salbutamolSalbutamolSalbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
(albuterol in USA) - bitolterol mesylate
- isoproterenolIsoproterenolIsoprenaline or isoproterenol is a medication used for the treatment of bradycardia , heart block, and rarely for asthma...
- levalbuterolLevalbuterolLevosalbutamol or levalbuterol , trade name Xopenex, is the R-enantiomer of the short-acting β2-adrenergic receptor agonist salbutamol. It is marketed by Cipla as Levolin, & by axa named Axazest.-Uses:...
- metaproterenol
- formoterolFormoterolFormoterol or eformoterol is a long-acting β2-agonist used in the management of asthma and/or chronic obstructive pulmonary disease...
- salmeterolSalmeterolSalmeterol is a long-acting beta2-adrenergic receptor agonist drug that is currently prescribed for the treatment of asthma and chronic obstructive pulmonary disease. It is currently available as a dry powder inhaler that releases a powdered form of the drug...
- terbutalineTerbutalineTerbutaline is a β2-adrenergic receptor agonist.Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption has been obtained in advance.Terbutaline is currently used to delay...
- clenbuterolClenbuterolClenbuterol is a sympathomimetic amine used by sufferers of breathing disorders as a decongestant and bronchodilator. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier...
- salbutamol
- ritodrineRitodrineRitodrine is a tocolytic drug, was used to stop premature labor. It is available in oral tablets or as an injection, and is typically used as the hydrochloride salt, ritodrine hydrochloride...
(tocolyticTocolyticTocolytics are medications used to suppress premature labor . They are given when delivery would result in premature birth...
)
Antagonists
(Beta blockerBeta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s)
- butoxamine*
- First generation (non-selective) β-blockers
See also
- Other adrenergic receptors
- Alpha-1 adrenergic receptorAlpha-1 adrenergic receptorThe alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...
- Alpha-2 adrenergic receptorAlpha-2 adrenergic receptorThe alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...
- Beta-1 adrenergic receptorBeta-1 adrenergic receptorThe beta-1 adrenergic receptor , also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it...
- Beta-3 adrenergic receptorBeta-3 adrenergic receptorThe beta-3 adrenergic receptor , also known as ADRB3, is an beta-adrenergic receptor, and also denotes the human gene encoding it.-Function:Actions of the β3 receptor include:*Enhancement of lipolysis in adipose tissue....
- Alpha-1 adrenergic receptor
Interactions
Beta-2 adrenergic receptor has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Delta Opioid receptor
Delta Opioid receptor
The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as its endogenous ligands.-Function:...
, Sodium-hydrogen antiporter 3 regulator 1
Sodium-hydrogen antiporter 3 regulator 1
Sodium-hydrogen antiporter 3 regulator 1 is a regulator of Sodium-hydrogen antiporter 3. It is encoded by the gene SLC9A3R1. It is also known as ERM Binding Protein 50 or Na+/H+ Exchanger Regulatory Factor...
, AKAP12
AKAP12
A-kinase anchor protein 12 is an enzyme that in humans is encoded by the AKAP12 gene.-Interactions:AKAP12 has been shown to interact with Beta-2 adrenergic receptor.-Further reading:...
and Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
.