Adrenergic receptors are a type of receptor to which catecholamines are coupled. They are involved in various functions of the sympathetic nervous system, which involves fight and flight responses.
Next we will see more deeply the types and subtypes of these receptors, in addition to explaining what each one of them is involved in.
What are adrenergic receptors?
Adrenergic receptors, also called adrenoceptors, are receptors that couple to G proteins. The two substances that couple to them are norepinephrine and epinephrine, which are two catecholamines. They are also the place where some drugs of the beta-blocker type, β2 and α2 agonists, used to treat hypertension and asthma, among other medical conditions, are placed.
Many cells in the body contain adrenergic receptors, and catecholamines are attached to them that activate the receptor and induce stimulation of the sympathetic nervous system. This system is in charge of preparing the body for a flight or fight situation, causing the pupils to dilate, increasing the heartbeat and, in essence, mobilizing the necessary energy to survive the potentially dangerous or stressful situation.
History of these receivers
In the 19th century it was accepted that the stimulation of the sympathetic nervous system could involve various changes in the organism, as long as there were one or more substances that induce this activation. But it was not until the following century that this phenomenon would be proposed:
One hypothesis held that there were two different types of neurotransmitters that had some effect on the sympathetic nerves. Another argued that instead of having two types of neurotransmitters, there should be two types of detection mechanisms for the same neurotransmitter, that is, that there would be two types of receptors for the same substance, which would imply two types of responses.
The first hypothesis was proposed by Walter Bradford Cannon and Arturo Rosenblueth, who proposed the existence of two neurotransmitters. One, which would be the one that would stimulate, was called simpatin E (of “excitation”) and the other, which would be the one that would inhibit, was simpatin I (of “inhibition”).
The second proposal found support during the period from 1906 to 1913. Henry Hallett Dale had explored the effects of adrenaline, called adrenine at the time, injected into animals or into the human bloodstream. When injected, this substance increased blood pressure. When the animal was exposed to ergotoxin its blood pressure decreased.
Dale proposed the idea that ergotoxin induced paralysis of the myoneural motor junctions, that is, those parts of the body that are responsible for controlling blood pressure. He indicated that, under normal conditions, there was a mixed mechanism that induced both paralysis and its activation, causing either contraction or relaxation depending on environmental demands and organic needs, and that these responses were made based on whether a The same substance had affected one or the other system, involving two different types of responses.
Later, in the 1940s, it was discovered that substances chemically related to adrenaline could induce different types of responses on the body. This belief was strengthened by seeing that muscles had, in effect, two different types of mechanisms that could involve two different responses to the same compound. The responses were induced based on the type of receptors in which the adrenaline was placed, calling them α and β.
Types of receivers
There are two main groups of adrenoceptors, which are subdivided into 9 subtypes in total:
The α's are classified into α1 (a receptor coupled to Gq protein) and α2 (a receptor that couples to a Gi protein)
α1 has 3 subtypes: α1A, α1B and α1D
α2 has 3 subtypes: α2A, α2B and α2C
The β are divided into β1, β2 and β3. All three couple to Gs proteins, but the β2 and β3 receptors also couple to Gi proteins.
Circulatory function
Epinephrine reacts to both α and β adrenergic receptors, involving different types of responses carried out by the circulatory system. These effects include vasoconstriction, related to α receptors, and vasodilation, related to β receptors.
Although α-adrenergic receptors have been shown to be less sensitive to epinephrine, when they are activated with a pharmacological dose of this substance, they induce vasodilation mediated by β-adrenergics. The reason for this is that the α1 receptors are more peripheral than the β, and by means of this drug-dose activation, the substance receives the α before the β. High doses of epinephrine in the bloodstream induce vasoconstriction.
Subtypes
Depending on the location of the receptors, the muscular response to adrenaline is different. The contraction and relaxation of smooth muscles is generally low. Cyclic adenosine monophosphate has different effects on smooth muscle than it does on cardiac muscle.
This substance, when found in high doses, contributes to the relaxation of smooth muscle, also increasing contractility and heart beat in the cardiac muscles, an effect, at first glance, counterintuitive.
Α receptors
The different α receptor subtypes have actions in common. Among these common actions are, as main, the following:
Vasoconstriction.
Reduced mobility of smooth tissue in the gastrointestinal tract.
Some α agonist substances can be used to treat rhinitis, because they decrease the secretion of mucus. Α-antagonist substances can be used to treat pheochromocytoma, since they decrease the vasoconstriction caused by norepinephrine that occurs in this medical condition.
1. α1 receiver
The main action of α1 receptors involves smooth muscle contraction. They cause vasoconstriction of many veins, including those found in the skin, the gastrointestinal system, the renal artery, and the brain. Other areas where smooth muscle contraction can occur are:
Ureter
Different conductor.
Hairy muscles.
Pregnant uterus.
Urethral sphincter.
Bronchioles.
Veins of the ciliary body.
The α1 antagonists, that is, those substances that when coupled induce actions contrary to those that agonists would perform, are used to treat hypertension, inducing a decrease in blood pressure, and also benign prostatic hyperplasia.
2. α2 receiver
The α2 receptor couples to Gi / o proteins. This receptor is presynaptic, inducing negative feedback effects, that is, control, on adrenergic substances such as norepinephrine.
For example, when norepinephrine is released into the synaptic space, it activates this receptor, reducing the release of norepinephrine from the presynaptic neuron and, thus, preventing an overproduction that involves negative effects on the body as a whole.
Among the actions of the α2 receptor are:
Decrease the release of insulin in the pancreas.
Increase the release of glucagon in the pancreas.
Contraction of the sphincters of the gastrointestinal tract.
Control of the release of norepinephrine in the central nervous system.
Increase platelet aggregation.
Decrease peripheral vascular resistance.
Α2-agonist substances can be used to treat hypertension, since they lower blood pressure by increasing the actions of the sympathetic nervous system.
Antagonists for these same receptors are used to treat impotence, relaxing the muscles of the penis and promoting blood flow in the area; depression, since they raise the mood by increasing the secretion norepinephrine.
Β receptors
Β-receptor agonists are used for heart failure, since they increase the cardiac response in the event of an emergency. They are also used in circulatory shock, redistributing blood volume.
Beta antagonists, called beta-blockers, are used to treat cardiac arrhythmia, since they decrease the response of the sinoatrial node, stabilizing cardiac function. As with agonists, antagonists can also be used in heart failure, preventing sudden death related to this condition, which is usually due to ischemia and arrhythmias.
They are also used for hyperthyroidism, reducing excessive peripheral synaptic response. In migraine they are used to reduce the number of attacks of this type of headache. In glaucoma they are used to reduce the pressure inside the eyes.
1. β1 receptor
Increases cardiac response by increasing heart rate, conduction velocity, and stroke volume.
2. β2 receptor
The β2 receptor actions include:
Smooth muscle relaxation of bronchi, gastrointestinal tract, veins and skeletal muscle.
Lipolysis of adipose tissue (fat burning).
Uterus relaxation in non-pregnant women.
Glycogenolysis and gluconeogenesis.
Stimulates the secretion of insulin.
Sphincter contraction of the gastrointestinal tract.
Immunological communication of the brain.
Β2 agonists are used to treat:
Asthma: reduce contraction of the bronchial muscle.
Hyperkalemia: they increase the intake of cellular potassium.
Preterm labor: they reduce the contraction of the uterine smooth muscle.
3. β3 receptor
The actions of β3 include increasing lipolysis of adipose tissue and relaxation of the bladder.
Β3 receptor agonists can be used as drugs for weight loss, although their effect is still being studied and has been linked to a worrying side effect: tremors in the extremities.
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