Neurotransmitters

Nerve cells communicate with each other and with other cells through the secretion of biochemical substances called neurotransmitters ^{[5, 38, 41, 54]}.

Many neurons secrete more than one type of neurotransmitter ^{[38, 39, 41]}.

Certain neurotransmitters can have different actions on the same target cell. The response time is also variable.

Each terminal button contains several thousand vesicles ^[1], each of which is filled with approximately 10,000 neurotransmitter molecules ^{[4, 100, 136]}.

Neurotransmitters :

Neurotransmitter criteria :

Today, more than 50 substances that meet the criteria for neurotransmitters ^{[52, 82]} have been identified. These main criteria are as follows ^{[38, 39, 41]}:

• A neurotransmitter must be present in the presynaptic neuron.
• Its release must occur in response to presynaptic depolarization.
• There must be specific receptors for this neurotransmitter in the postsynaptic neuron.

Other molecules widespread in the body, such as ATP and nitric oxide, have been considered neurotransmitters ^{[57, 110]}, although they possess atypical properties.

Classification of neurotransmitters :

There are several classifications of neurotransmitters based on their biochemical structure and their action ^[10].

According to their structure :

Two main categories are generally distinguished according to their structure ^{[38, 41, 52]}: neuropeptides and small molecules.

Neuropeptides ^{[2, 57]} consist essentially of amino acid chains; they include a wide range of molecules with diverse effects, such as endorphins ^[76] and somatostatin ^[5]. They are synthesized in the soma.

Small molecules ^[38] group together the majority of classic neurotransmitters, such as acetylcholine ^[41], glutamate ^[38], GABA ^[48], and catecholamines ^[52]. They are primarily synthesized in the nerve endings and have a much faster action than neuropeptides.

Regardless of the site of neurotransmitter synthesis, the required enzymes are always synthesized in the cell body ^[80].

According to their action :

Neurotransmitters can be excitatory or inhibitory; they can also have a direct or indirect action on their receptors.

Neuromodulators :

While the primary role of neurotransmitters is to transmit nerve impulses from one nerve cell to another, neuromodulators ^[1] (which are also secreted by neurons) function to modify the operation and metabolism of the target cell over a significant duration. These neuromodulators generally affect a population of neurons and harmonize their functioning.

Neurohormones :

Neurohormones ^[1], such as certain catecholamines (epinephrine and norepinephrine), are substances released by nerve cells into the bloodstream; they thus act at a distance on target cells spread throughout the entire body.

A neurotransmitter can also function as a neuromodulator or neurohormone depending on its site of production and its diffusion.

Neurotransmitter receptors :

The neurotransmitters can only take effect at sites capable of binding them: receptors. ^[41].

Receptors are specific macromolecular structures found in particular regions of the plasma membrane of target cells.

Molecules that bind to and activate a receptor are called ligands or agonists. Substances capable of binding to a receptor and blocking it are called antagonists.

There are two types of receptors ^[41]:

Channel-linked receptors (also called ionotropic) ^{[4, 39]}, which allow for the direct and rapid action of neurotransmitters. These receptors open a channel, causing specific ionic diffusion and a direct, rapid change in the potential of the postsynaptic membrane.

Metabotropic receptors (G-protein coupled) ^{[4, 39]}, which determine slow synaptic responses produced by the G-protein and by intracellular second messengers.

The combination of receptors and the chemical substances that activate or inactivate them constitutes a major target for therapeutic drugs ^{[38, 41]} and most recreational drugs.