Adrenergic receptors: what are they, functions, and types?

This type of neuronal receptors interacts with catecholamines in the nervous system.

Adrenergic receptors are a type of receptor in which catecholamines are coupled to the nervous system.. They are involved in various functions of the sympathetic nervous system, which involves fight and flight responses.

Below we will take a closer look at the types and subtypes of these receptors, as well as explain what each is involved in.

What are adrenergic receptors?

The adrenergic receptors, also called adrenoceptors, are receptors that are coupled to G proteins.. The two substances that bind to them are noradrenaline and adrenaline, which are two catecholamines. They are also the site where some beta-blocker type drugs, 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 that activate the receptor and induce stimulation of the sympathetic nervous system are coupled to them. This system is responsible for preparing the body for a flight or fight situation, causing the pupils to dilate, the heartbeat to increase and, in essence, mobilizing the energy needed to be able to survive the potentially dangerous or stressful situation.

History of these receptors

In the 19th century, the idea was accepted that stimulation of the sympathetic nervous system could lead to various changes in the organism, provided that there were one or more substances that induced this activation. But it was not until the following century that it was proposed how this phenomenon occurred:

One hypothesis held that there were two different types of neurotransmitters that exerted some effect on the sympathetic nerves. Another held that instead of there being two types of neurotransmitters there should be two types of sensing mechanisms for the same neurotransmitter, i.e., 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 stimulate, was called sympathin E (for "excitation") and the other, which would inhibit, was sympathin I (for "inhibition").

The second proposal found support during the period from 1906 to 1913. Henry Hallett Dale had explored the effects of adrenaline, then called adrenine, 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 a paralysis of the myoneural motor junctions, i.e. those parts of the organismthat 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 activation of the same, causing either contraction or relaxation depending on environmental demands and organic needs, and that these responses were made depending on whether the same substance had influenced one or the other system, implying two different types of responses.

Later, in the 1940s, it was discovered that substances chemically related to adrenaline could induce different types of responses in the organism. This belief was strengthened by the realization that muscles had, in effect, two different types of mechanisms that could involve two different responses to the same compound. The responses were induced depending on the type of receptors on which the adrenaline was placed, calling them α and β.

Types of receptors

There are two main groups of adrenoceptorswhich are subdivided into 9 subtypes in total:

α are classified into α1 (a Gq protein-coupled receptor) and α2 (a receptor that is coupled 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 are coupled to Gs proteins, but the β2 and β3 receptors are also coupled to Gi proteins.

Circulatory function

Epinephrine reacts to both α-adrenergic and β-adrenergic receptors.receptors, involving different types of responses carried out by the circulatory system. Among these effects are vasoconstriction, related to α receptors, and vasodilation, related to β receptors.

Although it has been seen that α-adrenergic receptors are less sensitive to epinephrine, when these are activated with a pharmacological dose of this substance, they induce β-adrenergic-mediated vasodilation. The reason for this is that α1 receptors are more peripheral than β receptors, and through this activation with pharmacological dose receives the substance earlier to the α than to the β receptors. High doses of epinephrine in the bloodstream induce vasoconstriction..

Subtypes

Depending on the location of the receptors, the muscle response to adrenaline is different. Smooth muscle contraction and relaxation is generally low.. Cyclic adenosine monophosphate has different effects on smooth muscle than on cardiac muscle.

This substance, when found in high doses, contributes to smooth muscle relaxation, also increasing contractility and heart beat in cardiac musculature, an effect, at first glance, counterintuitive.

α-receptors

The different α-receptor subtypes have actions in common. Among these actions in common, the following are the main ones:

• Vasoconstriction.
• Reduction of smooth tissue motility in the gastrointestinal tract.

Some α agonist substances can be used to treat rhinitis, because they decrease mucus secretion. Substances α antagonists can be used to treat pheochromocytoma.since they decrease the vasoconstriction caused by norepinephrine that occurs in this medical condition.

1. Receptor α1

The main action performed by the α1 receptors receptors involves smooth muscle contraction.. They produce vasoconstriction of many veins, including those found in the skin, gastrointestinal system, renal artery and cerebral veins. Other areas where smooth muscle contraction may occur include:

• Ureter
• Vas deferens.
• Hairy muscles.
• Pregnant uterus.
• Urethral sphincter.
• Bronchioles.
• Ciliary body veins.

The α1 antagonists, i.e., those substances that when coupled induce actions opposite to those that would be performed by agonists, are used to treat hypertension, inducing a decrease in blood pressure, and also benign ciliary hyperplasia.and also benign prostatic hyperplasia.

2. α2 Receptor

The α2 receptor is coupled to Gi/o proteins. This receptor is presynaptic, inducing negative feedback effects, i.e. control, on adrenergic substances such as norepinephrine.

For example, when norepinephrine is released into the synaptic space, it activates this receptor, causing the release of norepinephrine from the presynaptic neuron to be diminished and, thus, preventing an overproduction of norepinephrine that would have negative effects on the organism as a whole.

Among the actions of the α2 receptor are:

• Decrease insulin release in the pancreas.
• Increasing the release of glucagon in the pancreas.
• Contraction of the sphincters of the gastrointestinal tract.
• Control of norepinephrine release in the central nervous system.
• Increase platelet aggregation.
• Decrease peripheral vascular resistance.

α2-agonist substances can be used to treat hypertension.They lower blood pressure by increasing the actions of the sympathetic nervous system.

Antagonists for these same receptors are used to treat impotence, relaxing penile muscles and favoring blood flow in the area; depression, since they elevate mood by increasing norepinephrine secretion.

β-receptors

β-receptor agonists are used for heart failure.They increase cardiac response in the event of an emergency. They are also used in circulatory shock, redistributing blood volume.

The β-antagonists, called beta-blockers, are used to treat cardiac arrhythmia, since they decrease the sinoatrial node response, stabilizing cardiac function. As with agonists, antagonists can also be used in heart failure, preventing sudden death related to this condition, which is often 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. Receptor β1

Increases cardiac response by increasing the heart beat, conduction velocity and heart volume.and the conduction velocity and systolic volume.

2. β2 Receptor

The actions of the β2 receptor 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 insulin secretion.
• Contraction of sphincters of the gastrointestinal tract.
• Immunological communication of the brain.

The β2 agonists are used to treat:

• Asthma: reduce bronchial muscle contraction.
• Hyperkalemia: increase cellular potassium uptake.
• Preterm labor: reduce uterine smooth muscle contraction.

3. Receptor β3

The actions of β3 include increase lipolysis of adipose tissue and bladder relaxation..

The β3 receptor agonists can be used as weight loss drugs, although their effect is still being studied and has been linked to a worrisome side effect: limb tremors.

Bibliographic references:

• Adán, A. and Prat, G. (2016). Psychopharmacology: mechanism of action, effect and therapeutic management. Barcelona, Spain. Marge Medica Books.