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

We will now look more closely at the types and subtypes of these receptors, as well as explaining what each of them is involved in.

What are adrenergic receptors?

Adrenergic receptors, also called adrenoceptors, are receptors that attach to G-proteins . The two substances that attach to them are noradrenaline and adrenaline, which are two catecholamines. They are also the site of some beta-blocker-type drugs, agonists β2 and α2, used to treat hypertension and asthma, among other medical conditions.

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 responsible for preparing the body for an escape or fight situation, causing the pupils to dilate, the heartbeat to increase and, in essence, mobilizing the energy needed to survive the potentially dangerous or stressful situation.

History of these receptors

In the 19th century it was accepted that the stimulation of the sympathetic nervous system could involve 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 two types of neurotransmitters there should be two types of detection mechanisms for the same neurotransmitter, that is, 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 Arthur Rosenblueth, who proposed the existence of two neurotransmitters. One, which would stimulate, was called sympathetic E (for “excitation”) and the other, which would inhibit, was sympathetic I (for “inhibition”).

The second proposal found support during the period from 1906 to 1913. Henry Hallett Dale had explored the effects of adrenaline, called adrenaline at the time, injected into animals or the human bloodstream. When injected, this substance increased blood pressure. When the animal was exposed to ergotoxin its blood pressure would drop.

Dale proposed the idea that ergotoxin induced paralysis of the myoneural motor joints , 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 activation of the same, causing either contraction or relaxation according to environmental demands and organic needs, and that these responses were made according to whether the same substance had affected one or the other system, implying two different types of response.

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

Types of receptors

There are two main groups of adrenoceptors , which are subdivided into 9 subtypes in total:

The α are classified as α1 (a receptor coupled to a Gq protein) and α2 (a receptor 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 receptor are also coupled to Gi proteins.

Circulatory function

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

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

Subtypes

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

This substance, when found in high doses, contributes to smooth muscle relaxation, also increasing contractility and heartbeat in the heart muscle, an effect, at first sight, counter-intuitive.

Receivers α

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

  • Vasoconstriction.
  • Reduced mobility of smooth tissue in the gastrointestinal tract

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

1. Receiver α1

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

  • Ureter
  • Deferent conduit.
  • Hairy muscles.
  • Pregnant uterus.
  • Urethral sphincter.
  • Bronchioles.
  • Ciliary body veins.

The antagonists α1, that is, those substances that when coupled induce actions contrary to those that the agonists would perform, are used to treat hypertension, inducing a decrease in blood pressure , and also benign prostatic hyperplasia.

2. Receiver α2

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

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

Among the actions of the receiver α2 are:

  • Decrease the release of insulin into the pancreas.
  • Increase 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.

The agonist substances from α2 can be used to treat hypertension , as 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 norepinephrine secretion.

Receivers β

The receptor agonists β are used for heart failure , as they increase the heart$0027s response in the event of an emergency. They are also used in circulatory shock, redistributing blood volume.

The antagonists β, called beta-blockers, are used to treat heart arrhythmia because they decrease the response of the sinoatrial node, stabilizing heart 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 arrhythmia.

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. Receiver β1

Increases the heart$0027s response by increasing the heart rate , driving speed and systolic volume.

2. Receiver β2

The actions of the recipient β2 include:

  • Smooth muscle relaxation of the bronchi, gastrointestinal tract, veins and skeletal muscle.
  • Lipolysis of adipose tissue (fat burning).
  • Relaxing the uterus in non-pregnant women.
  • Glycogenolysis and gluconeogenesis
  • It stimulates insulin secretion.
  • Gastrointestinal tract sphincter contraction.
  • Immune communication of the brain.

The agonists at β2 are used to treat:

  • Asthma: reduces bronchial muscle contraction.
  • Hypercalemia: increases cellular potassium intake.
  • Premature birth — reduces uterine smooth muscle contraction

3. Receiver β3

Among the actions of β3 are increasing lipolysis of adipose tissue and bladder relaxation .

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

Bibliographic references:

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