The adrenergic receptors (or adrenoceptors ) are the protein-coupled G receptor class that is the target of catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).
Many cells have these receptors, and the binding of catecholamines to receptors will usually stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupil, increasing the heart rate, mobilizing energy, and diverting blood flow from the non-essential organ to the skeletal muscle.
Video Adrenergic receptor
Histori
At the turn of the nineteenth century, it was agreed that sympathetic nervous stimulation could cause different effects on body tissues, depending on the stimulating conditions (such as the presence or absence of some toxins). During the first half of the 20th century, two major proposals were made to explain this phenomenon:
- There are (at least) two types of neurotransmitters released from the sympathetic nerve terminals, or
- There are (at least) two different types of detection mechanisms for one neurotransmitter.
The first hypothesis was championed by Walter Cannon and Arturo Rosenblueth, who interpreted many experiments to then suggest that there are two neurotransmitter substances, which they call sympathin E (for 'excitation') and sympathine I (for 'inhibition').
The second hypothesis found support from 1906 to 1913, when Henry Dale explored the effects of adrenaline (which he called adrenine at the time), injected into animals, at blood pressure. Usually, adrenaline will increase the blood pressure of these animals. Although, if the animal is exposed to ergotoxine, blood pressure decreases. He proposed that ergotoxine causes "selective paralysis of the myoneural junction of the motor" (ie those who tend to increase blood pressure) then reveals that under normal conditions there is a "mixed response", including mechanisms that relax the smooth muscle and cause blood pressure drops. This "mixed response", with the same compound causing contraction or relaxation, is conceived as a response of various types of junctions to the same compound.
This experiment was developed by several groups, including Marsh and colleagues, who in February 1948 demonstrated that a series of compounds that are structurally linked to adrenaline can also exhibit the effects of contraction or relaxation, depending on whether there are other toxins or not. This again supports the argument that muscles have two different mechanisms by which they can respond to the same compound. In June of that year, Raymond Ahlquist, Professor of Pharmacology at the Medical College of Georgia, published a paper on adrenergic nerve transmission. In it, he explicitly mentions different responses as a result of what he calls? receptors and? receptors, and that the only sympathetic transmitter is adrenaline. While the latter conclusion then proves to be wrong (now known as noradrenaline), its receptor nomenclature and the concept of two different types of dice mechanisms for one neurotransmitter remain. In 1954, he was able to combine his findings in textbooks, Drill Pharmacology in Medicine , and thus disseminate the role played by? and? receptor sites in adrenaline/noradrenaline cellular mechanisms. These concepts will revolutionize progress in pharmacotherapy research, enabling selective design of specific molecules to target medical illness rather than relying on traditional research into the efficacy of existing herbal medicines.
Maps Adrenergic receptor
Category
There are two main groups of adrenergic receptors ,? and ?, with multiple subtypes.
- ? receptor has subtype? 1 (receptor G q ) and? 2 (receptor G i ). Phenylephrine is a selective agonist of? receptors.
- ? receptor has subtype? 1 ,? 2 and? 3 . All three are related to the protein G s (though < 2 are also paired to G i ), which in turn is related to adenylate cyclase. Binding of the agonist leads to an increase in intracellular concentration of the second cAMP messenger. Downstream effectsors of cAMP include cAMP-dependent protein kinase (PKA), which mediates some intracellular events after hormone binding. Isoprenaline is a non-selective agonist.
Role in circulation
Epinephrine (adrenaline) reacts with both- and -adrenoreceptors, causing vasoconstriction and vasodilation, respectively. Although receptors are less sensitive to epinephrine, when activated at pharmacological doses, they replace vasodilation mediated by -adrenoreceptors because there are more peripheral receptors compared with -adrenoreseptor. The result is that high levels of circulating epinephrine cause vasoconstriction. However, the opposite is true in the coronary arteries, where? 2 response is greater than? 1 , resulting in an overall dilation with increased sympathetic stimulation. At a lower level of epinephrine circulation (physiologic epinephrine secretion) ,? -adrenoreceptor stimulation dominates since epinephrine has a higher affinity for adrenoreceptors? 2 than adrenoreceptors? 1 , producing vasodilation followed by decreased peripheral vascular resistance.
Subtype
The behavior of smooth muscles varies depending on the location of the anatomy. Contraction of smooth muscle/relaxation is generalized below. One important note is the differential effect of cAMP enhancement in smooth muscle versus heart muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and heart rate in cardiac muscle.
No receptor 1C . At one time, there was a subtype known as C, but was found to be identical to one of the previously discovered subtypes. To avoid confusion, the naming is continued with the letter D.
? receptor
? receptors have some of the same functions, but also individual effects. Common (or non-specific) effects include:
- Vasoconstriction of blood vessels
- Reduces smooth muscle motility in the gastrointestinal tract
? 1 receptor
? 1 -adrenergic receptor is a member of the protein receptor superfamily
Special actions of receptor " 1 mainly involve smooth muscle contraction.This causes vasoconstriction in many blood vessels, including the skin, gastrointestinal system, kidney (renal artery) and brain.Another area of ​​smooth muscle contraction is:
- ureter
- vas deferens
- hair (pili arrector muscle)
- the uterus (during pregnancy)
- urethral sphincter
- urothelium and lamina propria
- bronchioles (although relatively small in the relaxant receptor effect 2 on bronchioles)
- the ciliary blood vessels (stimulation causes midriasis)
Further effects include glycogenolysis and gluconeogenesis of adipose and liver tissue, as well as secretions of sweat glands and Na reabsorption of the kidneys.
Antagonists can be used primarily in hypertension, anxiety disorders, and panic attacks.
? 2 receptors
Receptor pair 2 to protein G i/o . This is a presinaptic receptor, causing negative feedback on, for example, norepinephrine (NE). When NE is released to the synapse, it returns to receptor 2 , causing less release of NE than presinaptic neurons. This reduces the effect of NE. There is also a 2 receptor on the neural terminal membrane of post-synaptic adrenergic neurons.
There are 3 subtypes that are very homologous from? 2 receptors :? 2A ,? 2? , and? 2C .
Specific actions of the receptor? 2 includes:
- inhibition of insulin release in the pancreas.
- induced glucagon release from the pancreas.
- gastrointestinal tract sphincter contractions
- Negative feedback in neural synapses - inhibition of norepinephrine (NE) presinaptic release in CNS
- increased platelet aggregation
- lower peripheral blood vessel resistance
? receptor
? 1 receptor
Specific actions of the receptor? 1 includes: Increase cardiac output by increasing heart rate (positive chronotropic effect), conduction velocity (positive dromotropic effect), stroke volume (by increasing contractility - positive inotropic effect), and myocardium relaxation rate, by increasing the absorption rate of calcium ions (positive lusitropic effect), which helps increase heart rate.
? 2 receptor
Receptor " 2 " binds epinephrine and is involved in the fight or flight response ".
Specific actions of the receptor? 2 includes the following:
- Plain muscle relaxation, e.g. in the bronchi, gastrointestinal tract (decreased motility), vasodilation of blood vessels, especially in the skeletal muscle (although the norepinephrine vasodilator effect is relatively small and overwhelmed by alpha adrenoceptor-mediated vasoconstriction).
- Lipolysis on adipose tissue.
- Anabolism in skeletal muscle.
- Relaxing a non-pregnant uterus
- Relaxing urinary muscle urethra detrusor
- Spread arteries to skeletal muscle
- Glycogenolysis and gluconeogenesis
- Stimulates insulin secretion
- Contract of the gastrointestinal sphincter
- Thickening secretions from the salivary glands. â € <â € <
- Inhibits the release of histamine from mast cells
- Increase the renin secretion of the kidney
- Relaxation of bronchioles (salbutamol, a? 2 agonist reduces bronchiole constriction)
- Engage in brain-immune communication
? 3 receptors
Specific actions of the receptor? 3 includes:
- Increased lipolysis in adipose tissue. ? 3 activating drugs can theoretically be used as a weight loss agent, but is limited by tremor side effects.
See also
- Beta adrenergic receptor kinase
- Beta adrenergic receptor kinase-2
References
Further reading
- Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Chapter 11: Noradrenergic Transmission". Pharmacology (5th ed.). Elsevier Churchill Livingstone. ISBN: 0-443-07145-4.
- Rang HP, Dale MM, Ritter JM, RJ Flower (2007). "Chapter 11: Noradrenergic Transmission". Rang and Dale Pharmacology (6th ed.). Elsevier Churchill Livingstone. p. 169-170. ISBNÃ, 0-443-06911-5.
External links
- Alpha receptors are illustrated
- Adrenergic Receptors
- "Adrenoceptors". IUPHAR Database from Receptor and Ion Channel . International Union of Basic and Clinical Pharmacology.
- Basic Neurochemistry:? - and? -Adrenergic Receptors
- A brief summary of the receptor functions 3
- Receptor activation theory
- Desensitization of receptor 1
- UMR Orientation Protein in Membrane protein/pdbid-2rh1 - 3D structure from? 2 adrenergic receptor on the membrane
Source of the article : Wikipedia
0 Comments